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Immunology and Cell Biology of Parasitic Diseases 2013

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Volume 2013 |Article ID 456352 |

Alicia Vázquez-Mendoza, Julio César Carrero, Miriam Rodriguez-Sosa, "Parasitic Infections: A Role for C-Type Lectins Receptors", BioMed Research International, vol. 2013, Article ID 456352, 11 pages, 2013.

Parasitic Infections: A Role for C-Type Lectins Receptors

Academic Editor: Luis I. Terrazas
Received09 Aug 2012
Accepted12 Oct 2012
Published27 Jan 2013


Antigen-presenting cells (APCs) sense the microenvironment through several types of receptors that recognize pathogen-associated molecular patterns. In particular, C-type lectins receptors (CLRs), which are expressed by distinct subsets of dendritic cells (DCs) and macrophages (MØs), recognize and internalize specific carbohydrate antigens in a Ca2+-dependent manner. The targeting of these receptors is becoming an efficient strategy for parasite recognition. However, relatively little is known about how CLRs are involved in both pathogen recognition and the internalization of parasites. The role of CLRs in parasite infections is an area of considerable interest because this research will impact our understanding of the initiation of innate immune responses, which influences the outcome of specific immune responses. This paper attempts to summarize our understanding of the effects of parasites’ interactions with CLRs.

1. Introduction

Lectins are a diverse group of mono- and multivalent proteins and glycoproteins of nonimmune origin that have selective affinity for a carbohydrate or a group of carbohydrates [1]. These proteins are widely distributed in plants, animals, and microorganisms. In animals, lectins have been identified in a great number of cells. Lectins are either embedded in intracellular or cell surface membranes or are present in a soluble form in the plasma. Inside cells, lectins are also found in the cytosol and in the nucleus. Animal lectins play a crucial role in both physiological and pathological processes. Specific interactions between lectins and complex carbohydrates (glycoproteins, glycolipids, polysaccharides, or proteoglycans) are involved in numerous basic phenomena, such as embryonic development, intracellular trafficking, cell-cell and cell-matrix recognition, cell homing, endocytosis, phagocytosis, inflammation, and the metastatic spread of cancer cells (Table 1) [2].

GroupMolecules structureFamily membersLigandsExpressionFunctionReference

MR Mannose, fucose, and
MoPh, retina DCs, LCs, Fbls, and kidneyPathogen recognition, antigen presentation, clearance of endogenous cytopathic molecules, and regulation of circulating hormones [314]
DC-SIGN Mannose, ICAM-3 Mesangial cells and CMs, MØ, and DCsPathogen recognition, antigen presentation, cell migration, and DC-T-cell interactions
C-typeType-I Type-II
SIGNR-1 Zymosan, mannans, and dextraniDCs spleen MZ, lymph node, and pMØClearance of blood borne antigens
Dentin1 β-glucansDCs, neutrophils, and splenic T cellsAntifungal host defense, induction of TNF-α, and regulation of T-cell proliferation
Dectin2 α-mannansMØ, DCsImpairment of UV-induced tolerance
mMGL1 GalMØ, DCsInternalization and antigen presentation, bind to CD45 to inhibit T cells
mMGL2 Sructure LexMØ, DCs Anti-inflammatory response
L-SIGNStructure Le(a,b,y)Liver sinusoidal endothelial cellsAntigen receptor

Lysosomal hydrolasesTransport Man-6-P containing acid hydrolases from the Golgi to endosomal/lysosomal compartments[1517]

FucoseLiver and kidneyModulation of cell functions[1822]

Sialic acids with N- and O-linked glycosylationsMyeloid and lymphoid cellsRegulation of cell signaling from leucocytes[23, 24]
10 members humans (3, 5, 6, 7, 8, 9, 10, 11, 14, 16)
Rodents Siglec-3, E, F, G, H
Endocytic receptors

Abbreviations: Tm: transmenbrane; MØ: macrophages; pMØ: peritoneal macrophages; Dcs: dendritic cells; iDCs: immature dendritic cells; MoPh: mononuclear phagocytes; Fbls: fibroblasts; LCs: langerhans cells; CMs: cardiomyocytes; Lex: Lewis x, a, b, and y structures; Gal: galactose; MR: mannose receptor; DC-SIGN: dendritic cell-specific ICAM-3-grabbing nonintegrin; SIGNR-1: SIGN-related 1; homologe DC-SIGN; mMGL: macrophage galactose type c-lectin; L-SIGN: liver/lymph node-specific ICAM-3 grabbing nonintegrin; CD-MPR: cation-dependent mannose 6-phosphate receptor; CI-MPR: cation-independent mannose 6-phosphate receptor; Man-6-P: mannose 6-phosphate; Man-P-GlcNAc: mannose 6-phisphate N-acetylglucosamine ester; AAA: Anguilla anguilla agglutinin; MsaFBP32: F-lectin present in striped bass (Morone saxatilis).

2. Structural Characteristics of C-Type Lectin Receptors

The CLRs constitute a superfamily of more than 1,000 proteins classified into 17 groups based on their phylogeny and domain organization. Most CLRs possess one or more carbohydrate recognition domains (CRDs) or C-type lectin-like domains (CTLDs). The CTLD is a conserved structural motif containing as two protein loops stabilized by two disulfide bridges at the base of each loop. The second loop is more flexible than the first and generally contains the ligand binding site. Most CLRs are membrane-associated receptors that are involved in antigen capture and presentation [25, 26]. Endocytosis mediated by CLRs is guided by their intracellular internalization motifs, whereas some CLRs contain ITIM (immunoreceptor tyrosine-based inhibitory motif)-or ITAM (immunoreceptor tyrosine-based activation motif)-like motifs in their cytoplasmic domains, illustrating the potential immune-suppression or immune-activation functions of these receptors (Figure 1) [27].

Based on the primary structure of their CRDs, their folding patterns, and their cation requirements, animal lectins can be classified into several families, including C-, F-, P-, and I-type lectins, galectin, pentraxin, and others (Table 1) [18]. However, the most important molecules from the CLR family include macrophage galactose-type C-type lectin (MGL), dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN), the mannose receptor (MR), DEC205, and Dectin-1 (Figure 1).

3. Role of C-Type Lectin Receptors in the Immune Response

The initial recognition of an invading pathogen by antigen-presenting cells APCs, such as macrophages (MØs) or dendritic cells (DCs), is crucial in determining the type of effector T cell that subsequently mediates an immune response [1, 2]. APCs are equipped with highly specialized receptors, including an array of pattern recognition receptors (PRRs), such as C-type receptors (CLRs) and Toll-like receptors (TLRs). These receptors play an important role in the activation/maturation of APCs upon binding with conserved pathogen structures known as pathogen-associated molecular patterns (PAMPs). In contrast to TLRs, CLRs recognize and internalize specific carbohydrate antigens expressed by pathogens and host tissues in Ca2+-dependent manner [18, 2527].

Protein-carbohydrate interactions have important roles in two distinct aspects of the immune response. These interactions are involved both in pathogen recognition and in the cellular interactions that lead to pathogen neutralization [28]. Lectin receptors play an important role in the innate immune response by recognizing and binding specific carbohydrate moieties (usually a nonreducing terminal monosaccharide or oligosaccharide) on the surface of potential pathogens through CRDs [1, 2]. CRDs, in combination with other domains, can recognize carbohydrate moieties and induce agglutination, immobilization, complement-mediated opsonization and lysis [25].

In this review, we focus on integral membrane C-type lectins and their participation in the recognition of glycosylated parasite antigens. Despite the presence of a highly conserved domain, C-type lectins are functionally diverse and have been implicated in various processes, including cell adhesion, tissue integration and remodeling, platelet activation, complement activation, pathogen recognition, endocytosis, and phagocytosis [3, 29, 30].

The importance of C-type lectins is highlighted by the fact that several pathogens and tumor antigens take advantage of these receptors to escape intracellular degradation and to suppress the generation of an efficient immune response [31]. Several studies have demonstrated that some C-type lectins may function as adhesion, signaling, or antigen-uptake receptors [3235], and these results are consistent with the fact that some CLRs are present on MØs and DCs, which play a role in the initial step of capturing the antigens containing carbohydrates [36].

Several CLRs have been shown to contribute to the loading of endocytosed antigens on MHC class I and class II, thereby facilitating effective antigen-specific CD4+ and CD8+ T-cell responses [37, 38]. There are evidence that some CLRs (like DC-SING, DC205, and Dectin-1) are able to trigger distinct signaling pathways that modulate cell functions through the expression of specific molecules and cytokines, in most cases promote the antigen presentation and determining the polarizations of T cells [4, 39]. However, most evidence about CLR trigger signaling pathways have emerged using virus, bacterial pathogens, fungus, or peptides. There are not evidence about the interaction of parasites with CLRs and activation of a signaling pathway.

The signaling through MGL is emerging recently, using DCs, has been demonstrated that MGL engagement to anti-MGL antibody or triggered the phosphorylation of ERK1,2 and the activation of NF-kB signal promoting DC activation and increase in antigen-specific CD8+ T-cell activation; however, the effects of this activation are strongly dependent on the type of stimulus added to the cells [5].

Moreover, several studies suggest that CLRs may also modulate immune reactions through cross-talk with other receptors, especially TLRs. These results indicate that the outcome of an immune response is determined by the balance between triggering the two receptors families [5, 40]. Many transmembrane C-type lectins belonging to groups II, V, and VI are expressed primarily by myeloid cells. Although many are “orphan” receptors, others have been shown to promote the phagocytosis of nonopsonized microbes and to induce cytokine production in MØs and DCs, leukocytes that play critical roles in innate immunity and in the subsequent modulation of adaptive immune responses [41]. These properties make the C-type lectin family an optimal tool for APCs to target parasites.

4. C-Type Lectins in Parasitic Infection (Table 2)

ParasiteReceptorModelIn vivo/in vitro Role Reference

L. donovani MRBALB/c micein vivo/ in vitro Uptake of mannose containing glycoconjugates[48]
MRSwiss albino micein vitro Binding promastigotes[36]
MRhmDMØin vitro Attachment and ingestion promastigotes[49]
L. amazonensis MRSkin Fblsin vitro Uptake of mannosylated ligands[6]
L. major MRBMDMs
MR-KO mice
in vivo Recognizes mannose residues on the surface Leishmania, but it’s not essential for host defense[45]
L. pifanoi DC-SIGNMDDCs
cell line K562
in vitro Binding and internalization of amastigotes[50]
L. pifanoi  
L. infantum
cell lineK562
in vitro Receptor for promastigotes and amastigote infective stages from both visceral and cutaneous leishmaniasis[51]
T. cruzi   
Tulahuen strain
MRBALB/c mice
Cell line J774 (MØ)
in vivo/in vitro Bind to Cz, increasing MR recycling which leads to arginase activity[46]
 Y and DM strainsMRCM and MØin vitro Adhesion and uptake of parasites[52]
T. brucei MGLC57BL/6 mice
BALB/c mice
in vivo Marker of aaMØ[53]
T. muris MRC57BL/6 MR-KO micein vivo/in vitro Recognized components E/S of parasites[47]
S. mansoni MGLCell lines SW948,
SKBR3, ZR75-1
CHO, BLM, FM3.29
FM6, SK23mel
in vitro Recognized LDN and LDNF glycans[54]
MGLHuman DCsin vitro Internalization of glycolipids of SEA[55]
DC-SIGNHuman DCsin vitro Adhesion to glycolipids of SEA[7]
DC-SIGNHuman DCsin vitro Recognize glycans of SEA[56]
L-SIGNCell line K562in vitro Binds to structures Lea,b,y of SEA[8]
L-SINGCell line K562in vitro Binds and internalization of SEA[57]
in vivo/in vitro Recognize antigens of AWA and SEA[9]
Dectin-2C57BL/6in vivo/in vitro Binds SEA component[58]
MRC57BL/6 WT or
in vivo/in vitro Internalization E/S material by schistosome larvae[59]
T. crassiceps
Human DCsin vitro TcES positively modulated the expression of MGL but negatively modulated DC-SIGN[60]

Abbreviations: MR: mannose receptor; DC-SIGN: dendritic cell-specific ICAM-3 grabbing nonintegrin; SIGNR-1: SIGN-related 1; homologe DC-SIGN; mMGL: macrophage galactose type c-lectin; L-SIGN: liver/lymph node-specific ICAM-3 grabbing nonintegrin; Fbls: fibroblasts; BMDMs: bone marrow-derived macrophages; MDDCs: monocyte-derived dendritic cells; IMDDCs: immature monocyte-derived DCs; MØ: macrophages; CM: cardiomyocyte; Cz: cruzipaina; E/S: excretory/secretory; LDN: [GalNAcβ1–4GlcNAc-R]; LDNF: [GalNAcβ1–4(Fucα1–3)GluNAc-R]; SEA: soluble egg antigens; Le: structures of Lewis; AWA: adult worm antigen; TcES: Taenia crassiceps excreted-secreted antigens.

A number of glycan moieties have been identified in most parasites that potentially bind various CLRs, which act as sensors of the innate immune system.

4.1. Protozoa
4.1.1. Leishmania

The trypanosomatid flagellates of the genus Leishmania cause diverse diseases with varying clinical symptoms and underlying pathologies. These diseases include visceral leishmaniasis (Kala-azar), mucocutaneous leishmaniasis, cutaneous leishmaniasis, and post-Kala-azar dermal leishmaniasis (PKDL) [42].

These diseases cause significant morbidity and mortality in the 98 countries or territories, where they are endemic [43]. Leishmania have two developmental stages: the promastigote, which is an extracellular flagellated form that is transmitted by insect vectors, and the amastigote, which is an intracellular multiplicative form that multiplies within the phagocytes of the vertebrate host, a process that involves different ligand-receptor systems [44]. The repetitive structure and glycan modifications associated with many Leishmania cell surface molecules suggest that these parasites may interact with CLRs, for example, MR and DC-SIGN [6, 45].

Mannose Receptor (MR). MR is a C-type lectin. It is a transmembrane glycoprotein (175 kDa) with eight C-type-lectin-like domains (or carbohydrate-recognition domains, CRDs) that is expressed on the surface of several cell types, such as MØs, DCs, and some epithelial cells. MR mediates the binding and internalization of mannosylated glycoproteins and participates in the endocytosis of different pathogens bearing mannose residues on their surfaces [6, 46, 47].

Previous studies both in vivo and in vitro have demonstrated the involvement of MR during the recognition and internalization of promastigotes of different Leishmania species (donovani, amazonensis). Mouse peritoneal MØs infected with L. donovani exhibited a decrease in MR activity, with a loss of 50% of original binding activity after 4 days of infection. A possible explanation for this decrease in the expression of MR is the direct correlation with the number of amastigotes within MØs and the recovery of MR activity after the elimination of parasites from MØs after treatment with methotrexate/mL conjugated with bovine serum albumin modified with mannose (Man-BSA) for 3 h [48]. Competition assays with different MR ligands (Man-BSA or D-mannose) revealed an important decrease in the activity of MR, with a loss between 50% to 80% in phagocytic capacity, demonstrating the participation of MR during parasite recognition and the upregulation of MR expression during the initial steps of the infection [6, 35, 48, 49].

A recent study showed that bone marrow-derived macrophages (BMDMs) infected with L. major metacyclic promastigotes exhibit TNF-α and IL-12 production levels similar to those in MR-wild-type (MR-WT) mice and MR-knockout (MR-KO) mice. The clinical course of L. major and L. donovani infections was slightly different with respect to the area covered by lesions between the MR-WT and MR-KO mice at week 7. However, the levels of ulcer healing and the resolution of the lesions were equivalent. Moreover, assays measuring the activation of MAPKs (ERK1/2, p38, and JNK) revealed that MR is not necessary for the inhibition of ERK and p38 activation. In addition, immunohistochemical analysis of cutaneous lesions from MR-KO and MR-WT mice revealed no differences in lesion architecture or cell components. Together, these data suggest that MR is not essential for host resistance against Leishmania infections and that either redundant MØ receptors compensate for the lack of MR or MR does not play a role in parasite attachment [45].

Dendritic Cell-Specific Intercellular Adhesion Molecule-3-Grabbing Nonintegrin (DC-SIGN). Also known as CD209, DC-SIGN is a type II transmembrane CLR that is expressed on DCs and involved in cell-cell interactions through its capacity to bind ICAM-3 and ICAM-2 [50, 61]. This receptor is used by protozoan parasites of the genus Leishmania. Previous studies have investigated possible Leishmania/DC-SIGN interactions through the use of fluorescence-labeled parasites in combination with blocking agents such as anti-DC-SIGN antibodies and soluble mannan. These studies showed that DC-SIGN is a receptor for the promastigotes and amastigotes of both the visceral (L. infantum) and cutaneous (L. pifanoi) forms but not for Leishmania major metacyclic promastigotes, suggesting that DC-SIGN is a broad Leishmania receptor that exhibits variable affinity for distinct infective forms and species of the parasite [50, 51]. There is no doubt that these findings are important; however, it remains to be determined whether this recognition influences the immune response to Leishmaniasis.

4.1.2. Trypanosoma cruzi

The protozoan parasite Trypanosoma cruzi (T. cruzi), the etiological agent of human Chagas disease, is endemic in Latin America, where 18–20 million of people are infected [62]. Infection leads to an acute phase that may last between 2 and 4 months and is characterized by high numbers of parasites in the bloodstream and tissues. The control of parasite replication leads to chronic, often life-long disease. Most individuals in the chronic phase have a silent, asymptomatic clinical form of Chagas’ disease and are classified as indeterminate patients [63]. However, approximately 30% of chronically infected individuals develop a severe clinical form in which digestive and/or cardiac alterations often lead to death [6467].

During the process of parasite internalization, the interaction between receptors expressed in the host cell and the parasite is important because these receptors are responsible for recognizing the major antigens of T. cruzi. This parasite expresses mucin-like glycoproteins (TcMUCs) on its membrane. These proteins are highly glycosylated glycoconjugates (approximately 60% of their weight is carbohydrates) and are threonine-rich, serine- and proline-rich polyanionic molecules that are anchored to the plasma membrane through glycosylphosphatidylinositol [64, 68, 69].

Furthermore, T. cruzi contains a major lysosomal cysteine proteinase called cruzipain (Cz), one of the immunodominant antigens of T. cruzi. Cz is a glycoprotein of approximately 52–58 kDa and has both high mannose and complex type-N-linked glycans in the C-terminal domain. It is expressed in all stages of the parasite and is highly immunogenic in humans. Moreover, it has been shown that Cz induces the alternative activation of MØs in vitro and upregulates arginase activity. This activation profile was shown to be associated with the functional ability of these cells to promote the intracellular growth of T. cruzi [46].

Mannose Receptor (MR). Enzyme binding assays using HRP (horseradish peroxidase) as the mannosylated ligand, which were used to characterize the cardiomyocyte mannose receptor (CM-MR) and its involvement in T. cruzi invasion, demonstrated that after the infection of cardiomyocytes (CM) with T. cruzi, a considerable reduction in HRP binding was noticed. Binding was almost completely restored by treating the infected cultures with the trypanocidal drug nifurtimox [52]. These results showed that CM-MR participated in the adhesion and uptake of T. cruzi by CM.

Another study found that T. cruzi-infected MØs pre-incubated with mannose-bovine serum albumin (Man-BSA, MR specific ligand) exhibited high levels of urea, increased intracellular amastigote growth, the downregulation of JNK and p44/p42 phosphorylation, and an increase in p38 MAPK phosphorylation relative to control cells. In addition, MØs incubated with Cz or Man-BSA exhibited enhanced MR recycling. However, T. cruzi-infected peritoneal MØs incubated with an MR-blocking antibody showed reductions in arginase activity and intracellular parasite growth. Moreover, the level of MR on peritoneal cells from T. cruzi-infected BALB/c mice at 13 and 15 days after-infection has been evaluated, and flow cytometry analysis revealed an increase in F4/80+ MR+ cells as the infection progressed. Together, these results showed that the interaction with MR on MØs may be a mechanism by with T. cruzi evades the innate immune response both in vitro and in vivo [46].

4.1.3. Trypanosoma brucei

The protozoan parasite Trypanosoma brucei (T. brucei) is the causative agent of the human and animal African trypanosomiasis, which is frequently fatal if not treated. This parasite has a digenetic life cycle, replicating in the alimentary canal of its vector, the tsetse fly, and in the bloodstream of mammals. In the mammalian host, the bloodstream form of T. brucei lives and divides extracellularly in the blood, lymph, and interstitial fluids [70, 71]. The bloodstream form of T. brucei is rich in galactose-containing glycoproteins, most notably the abundant variant surface glycoprotein (VSG), which protects the parasite from the complement pathway and undergoes antigenic variation to evade specific immune responses [72].

Macrophage Galactose Type C-Lectin (MGL). MGL is a member of the type II family of C-type lectins and has an approximate molecular mass of 42 kDa. MGL is expressed on immature human and mouse DCs and MØs in the skin and lymph nodes [27, 73]. Mice contain two functional copies of the MGL gene, mMGL1 and mMGL2 [74], which are both expressed by dermal DCs and MØs [53, 75], whereas in humans, only one MGL gene is found [76]. mMGL1 and mMGL2 have different carbohydrate specificities: mMGL1 is specific for Lewis X ( ) and structures, whereas mMGL2, similar to hMGL, recognizes α/β-GalNAc structures and galactose, including O-linked Tn-antigen, TF-antigen, and core 2 structure [54, 77]. In the skin, MGL is a marker for CD1a+ dermal DCs, a cell type with enhanced ability to stimulate naive T cells relative to other dermal APC subsets.

Raes et al. report that mMGL1 and mMGL2 are induced in peritoneal MØs during in vivo infection with T. brucei, correlating with a switch from a type I cytokine environment in the early stage of infection to a type II cytokine environment in the late and chronic phases. In addition, it has been demonstrated that the incubation of thioglycolate-elicited peritoneal MØs with IL-4 o IL-13 moderately induced mMGL1 expression and strongly induced mMGL2 expression, but IFN-γ did not [53]. The results presented in this paper suggest that the mMGL1 and mMGL2 receptors are novel markers for type II cytokine-dependent alternatively activated macrophages (aaMØ) both in vitro and in the chronic phase of infection with T. brucei. These findings are important, but the possible interaction between antigens of T. brucei and mMGL remains to be defined, as does the role of mMGL in the immune response.

4.2. Nematodes
4.2.1. Trichuris muris

Several gastrointestinal nematodes have been reported to express ligands for MR on their surface. Trichuris muris (T. muris) is a natural mouse model of the gastrointestinal nematode parasite Trichuris trichiura (T. trichiura), one of the most prevalent human helminth infections. Studies of the role of cells in immune responses to T. muris and the mechanisms of immune expulsion of these worms from mice have demonstrated that B cells and antibodies are required for resistance to thisparasite. The evasion of the immune response by T. muris causes chronic infection, which has the ability to manipulate the host immune system. T. muris excretory/secretory (E/S) products from a heterogeneous solution of worm proteins contain substances that have been shown to bear mannose and N-acetylglucosamine residues; therefore, these substances are potential ligands for C-type lectin receptors such as MR [78].

Deschoolmeester et al. showed in vitro that MR-KO-derived bone-marrow-derived MØs (BMDMs) expressed similar levels of several cytokines when exposed to T. muris E/S. The only difference observed was a reduction in the production of IL-6 by alternatively activated BMDMs in the absence of MR, and the infection of MR-KO mice revealed the expulsion of T. muris with the same kinetics as observed for WT animals and a similar cytokine response in the draining mesenteric lymph nodes. Moreover, there were no differences in MØ recruitment, the ability of MØs to become alternatively activated, goblet cell hyperplasia, or gross crypt pathology during infection. In summary, MR binds to components of T. muris, but it is not required for the development of an immune response leading to the expulsion of T. muris [47].

4.3. Helminths: Trematodes
4.3.1. Schistosoma mansoni

Parasitic helminths express various carbohydrates containing glycoproteins on their surface and release glycan-rich E/S products that can potentially bind to various CLRs [59]. The parasite helminth Schistosoma mansoni (S. mansoni) is the causative agent of the chronic disease schistosomiasis, which is the second most prevalent human parasitic disease, affecting ~300 million people worldwide, particularly in tropical countries [55, 79]. Immunologically, S. mansoni infection is dominated by two distinct Th phases: an initial Th1 (IFN-γ) response, which switches to a stronger Th2 (IL-10, IL-5, and IL-13) response [58]. One of the most striking features of schistosomiasis is that the worms are experts in modulating and evading the host immune response, enabling their survival, migration, and development in different host tissues. Schistosomal glycoconjugates (glycoproteins and glycolipids) have shown to play important roles in host-parasite interactions. These glycoconjugates are often developmentally regulated antigens that are expressed during different life cycle stages. Some studies have indicated that antigens Galβ1,4(Fucα1–3)GlcNAc have important roles in host-schistosome interactions. ( ) antigens have been found in glycoconjugates from all life cycle stages, including the membrane-bound glycoproteins of adult schistosomes and secreted egg and gut glycoproteins [7].

Macrophage Galactose Type C-Lectin (MGL). Human MGL has an exclusive specificity for terminal GalNAc residues, such as those found in the glycoproteins of the helminth parasite S. mansoni, in filoviruses, and in tumor-associated antigens [80].

Binding assays revealed that MGL recognizes both terminal β-GalNAc residues of LDN [GalNAcβ1–4GlcNAc-R] and LDNF [GalNAcβ1–4(Fucα1–3)GlcNAc-R] glycans present in SEA of S. mansoni. The specific interaction between MGL and SEA glycoproteins containing LDN and LDNF demonstrates that MGL functions as a pattern recognition receptor for S. mansoni [54].

In another study using binding assays and blocking antibodies reported that SEA of S. mansoni is internalized by human DCs through MGL. Moreover, the confocal laser scanning microscopy reveals colocalization of SEA with MHC-II in the lysosomal compartments suggests that Ag processing and presentation can occur. Certainly these findings are important, however remains to be answered if this recognition leads to antigen presentation and modulation of the immune response to S. mansoni [55].

DC-SIGN. It has been demonstrated that the blockade with monoclonal antibodies against the carbohydrate antigens and LDNF inhibit the binding of DC-SIGN to soluble egg antigens (SEAs). The glycoproteins several SEAs from different schistosome species (S. mansoni, S. haematobium, and S. japonicum) contain ligands for DC-SIGN. It has also been demonstrated that a specific mutation in the carbohydrate-recognition domain (CDR) of DC-SIGN abrogates binding to either SEAs or [56].

Structural characterization of the glycolipids and the study of cellular binding revealed that DC-SIGN binds to the carbohydrate moieties of glycosphingolipids with and structure [Fucα1-2Galβ14(Fucα1–3)GlcNAc] moieties. DC-SIGN recognizes not only the self-glycan ligand within cercarial glycolipids, but also glycolipids carrying pseudo- , a nonself-structure that to date has been found within Schistosome cercarial (S. cercarial) glycolipids and ES products [7]. These results show that DC-SIGN recognizes and antigens present in the SEAs and glycolipids of S. cercarial. Thus, DCs likely interact with Schistosomes early during infection through this lectin. However, more studies are needed to determine whether the recognition of glycosylated antigens through DC-SIGN is involved in resistance or susceptibility to S. mansoni infection in vivo.

L-SIGN. Liver/lymph node-specific ICAM-3-grabbing nonintegrin (LSIGN/CD209L/DC-SIGN-R) is a human homolog of DC-SIGN. L-SIGN shares 77% amino acid sequence identity with DC-SIGN and is expressed on liver sinusoidal endothelial cells (LSECs), which function as antigen-presenting cells in the liver [81].

L-SIGN, a highly related homolog of DC-SIGN, can bind both schistosome egg antigens (SEAs) and glycosphingolipids and can mediate the internalization of SEAs. However, binding assays showed that L-SIGN recognizes a glycoprotein fraction different from that recognized by DC-SIGN. It has been demonstrated that L-SIGN does not bind to neoglycoconjugates carrying but does recognize other fucosylated glycans, that is, . Other studies have demonstrated that the glycosylation of schistosome antigens plays an important role in immunological process during schistosome infection [8, 57]. Those studies confirmed that L-SIGN recognizes both oligomannosidic N-glycans and multiply fucosylated carbohydrate motifs within SEAs. In addition, these studies demonstrated that L-SIGN can recognize a broad but specific glycan profile.

SIGNR1. Also called CD-209b, is one of the eight mouse homologs of human DC-SIGN and is expressed on particular MØ subsets in the marginal zone of the spleen and the medulla of the lymph nodes and on the peritoneal MØs. SIGNR1 recognizes glycans from different pathogens and has been shown to bind and -containing carbohydrates [82, 83].

An in vitro studyusing cells transfected with SIGNR1 showed that glycans from both SEAs and schistosome worm antigens were bound by SIGNR1 in a dose-dependent manner, demonstrating the ability of SIGNR1 to recognize and bind to two different stages of the parasite. However, the in vivo infection of SIGR1-deficient BALB/c mice (SIGNR-KO) with 25 cercariae of Schistosoma revealed that SIGNR1 has no role in primary or secondary pulmonary granuloma induced by schistosome eggs. SIGNR-KO mice exhibited unaltered worm fecundity, and the fecal eggs and the size and eosinophil content of the granulomas surrounding eggs in the liver were comparable, as were the levels of hepatic fibrosis. Moreover, no differences in the cytokine the production by spleen cells were observed. In conclusion, although SIGNR1 can recognize S. mansoni antigens in vitro, this receptor does not have a functional role in vivo during infection [9].

Dectin-2. Dectin-2 is a member of the C-type lectin family and has single complementarity-determining region (CRD). This protein expressed mainly in MØs and DCs. Dectin-2 recognizes α-mannans and transduces the signal through an association with the ITAM-containing Fc receptor γ chain [84, 85].

In vitro restimulation assays using spleen and MLN cells with SEA (20 μg/mL) have demonstrated that SEA associates with Dectin-2 and Fc receptor γ-chain (FcRγ) receptors. Moreover, SEA-mediated IL-1β production was significantly inhibited when BMDCs were pretreated with Dectn-2-specific antibodies or when Dectin-2-deficient BMDCs were used. In contrast, TNF-α production was not impaired. Thus, different components within SEAs mediate different immune reactions. These observations suggest that SEA triggers the Dectin-2 receptor, which couples with FcRγ chain, to activate the Syk-kinase signaling pathway, which controls IL-1β release in an ROS- and potassium efflux-dependent manner, the Nlrp3 inflammasome activation, and IL-1β release. However, even though these findings are important, it is necessary to determine whether this receptor plays a key role during infection in vivo [58].

Mannose Receptor (MR). It has been demonstrated that infective larvae of the parasitic helminth S. mansoni contain a large number of glycosylated components specific for MR. MR ligands are particularly rich in excretory/secretory (E/S) material released during the transformation of cercariae into schistosomula, a process that is critical for infection of the host. E/S material from carboxyfluorescein diacetate succinimidyl ester (CFDA-SE)-labeled cercariae showed enhanced binding by Chinese hamster ovary cells (CHO) lines transduced to express MR and by an MØ cell line that overexpresses MR (J774E) relative to the level of binding by WT CHO cells. Conversely, uptake was significantly lower by bone marrow-derived macrophages (BMDM) from MR-KO mice, although these cells were more active as judged by the enhanced proinflammatory cytokine production and CD40 expression. After natural percutaneous infection of MR-KO mice with CFDA-SE-labeled parasites, there were fewer cells in the skin and draining lymph nodes that were CFDA-SE(+) relative to the numbers in WT mice, indicating that there was reduced uptake and presentation of larval parasite antigens. However, the antigen-specific proliferation of skin-draining lymph node cells was significantly enhanced, and these cells secreted markedly elevated levels of IFN-γ but decreased levels of IL-4. These results demonstrated that MR on mononuclear phagocytic cells plays a significant role in internalizing E/S material released by the invasive stages of the parasite, which in turn modulates the production of proinflammatory cytokines. In the absence of MR, antigen-specific CD4+ cells are Th1 biased, suggesting that the ligation of MR by glycosylated E/S material released by schistosome larvae modulates the production of IFN-γ by CD4+ cells [59].

4.4. Helminths: Cestodes
4.4.1. Taenia crassiceps

Taenia crassiceps (T. crassiceps) is a tapeworm that is found in wild and domestic animals but does not cause clinical disease in nonimmunocompromised humans. This parasite has been used as an experimental model for cysticercosis [86]. Previous studies demonstrated that soluble antigens from T. crassiceps are highly glycosylated and are responsible for Th2 polarization in vivo [87, 88]. One study found that the excretory/secretory products of the cestode T. crassiceps (TcESs) do not induce the maturation of human DCs, as demonstrated by the lack of increase in the expression levels of CD83, HLA-DR, CD80, and CD86. TcESs enhanced the production of IL-10, positively modulated the expression of mMGL and negatively modulated the expression of DC-SIGN, although the source of these antigens is not a human parasite. These results showed that TcESs induce a tolerogenic-like phenotype in human DCs and modulate the expression of PRRs involved in key functions of DCs such as mMGL and DC-SIGN. This modulation is a possible mechanism used by T. crassiceps to modify the phenotype and hence the functions of human DCs, directing the balance toward immune suppression and allowing the survival of this parasite [60].

5. Conclusion

All studies described above demonstrate that CLRs are essential to the recognition of different carbohydrates present on surface or in the excretory/secretory products of different parasites. This recognition can promote the uptake, internalization and processing of parasite antigens that can influence the immune response. However, little is known about the role of CLRs in the immune response to parasitic infections. Future studies are needed to understand the immune mechanisms underlying the interaction of parasite antigens with CLRs.


The authors thank M. S. Imelda Juarez for collecting the items required for this paper. National Council of Science and Technology (CONACYT)-Mexico supported PhD fellowship for A. Vázquez-Mendoza and this review is a requirement to obtain his degree in Biomedical Sciences, UNAM. The author’s research was supported by the Grants ICYT-DF-317-2010, UNAM-DGAPA-PAPIIT-IN212412, PAPCA-23-2012 and by the CONACYT-152224.


  1. I. West and O. Goldring, “Lectin affinity chromatography,” Methods in Molecular Biology, vol. 244, pp. 159–166, 2004. View at: Google Scholar
  2. E. Duverger, N. Lamerant-Fayel, N. Frison, and M. Monsigny, “Carbohydrate-lectin interactions assayed by SPR,” Methods in Molecular Biology, vol. 627, pp. 157–178, 2010. View at: Publisher Site | Google Scholar
  3. A. M. Kerrigan and G. D. Brown, “C-type lectins and phagocytosis,” Immunobiology, vol. 214, no. 7, pp. 562–575, 2009. View at: Publisher Site | Google Scholar
  4. T. B. H. Geijtenbeek and S. I. Gringhuis, “Signalling through C-type lectin receptors: shaping immune responses,” Nature Reviews Immunology, vol. 9, no. 7, pp. 465–479, 2009. View at: Publisher Site | Google Scholar
  5. C. Napoletano, I. G. Zizzari, A. Rughetti et al., “Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation,” European Journal of Immunology, vol. 42, pp. 936–945, 2012. View at: Google Scholar
  6. R. C. Hespanhol, M. D. N. C. Soeiro, M. B. Meuser, M. D. N. S. L. Meirelles, and S. Côrte-Real, “The expression of mannose receptors in skin fibroblast and their involvement in Leishmania (L.) amazonensis invasion,” Journal of Histochemistry and Cytochemistry, vol. 53, no. 1, pp. 35–44, 2005. View at: Publisher Site | Google Scholar
  7. S. Meyer, E. Van Liempt, A. Imberty et al., “DC-SIGN mediates binding of dendritic cells to authentic pseudo-Lewis Y glycolipids of Schistosoma mansoni cercariae, the first parasite-specific ligand of DC-SIGN,” Journal of Biological Chemistry, vol. 280, no. 45, pp. 37349–37359, 2005. View at: Publisher Site | Google Scholar
  8. E. Van Liempt, A. Imberty, C. M. C. Bank et al., “Molecular basis of the differences in binding properties of the highly related C-type lectins DC-SIGN and L-SIGN to Lewis X trisaccharide and Schistosoma mansoni egg antigens,” Journal of Biological Chemistry, vol. 279, no. 32, pp. 33161–33167, 2004. View at: Publisher Site | Google Scholar
  9. S. P. Saunders, C. M. Walsh, J. L. Barlow et al., “The C-type lectin SIGNR1 binds Schistosoma mansoni antigens in vitro, but SIGNR1-deficient mice have normal responses during schistosome infection,” Infection and Immunity, vol. 77, no. 1, pp. 399–404, 2009. View at: Publisher Site | Google Scholar
  10. E. P. McGreal, L. Martinez-Pomares, and S. Gordon, “Divergent roles for C-type lectins expressed by cells of the innate immune system,” Molecular Immunology, vol. 41, no. 11, pp. 1109–1121, 2004. View at: Publisher Site | Google Scholar
  11. T. B. H. Geijtenbeek, S. J. Van Vliet, A. Engering, B. A. 'T Hart, and Y. Van Kooyk, “Self- and nonself-recognition by C-type lectins on dendritic cells,” Annual Review of Immunology, vol. 22, pp. 33–54, 2004. View at: Publisher Site | Google Scholar
  12. S. J. van Vliet, E. Saeland, and Y. van Kooyk, “Sweet preferences of MGL: carbohydrate specificity and function,” Trends in Immunology, vol. 29, no. 2, pp. 83–90, 2008. View at: Publisher Site | Google Scholar
  13. J. Sabatte, W. Faigle, A. Ceballos et al., “Semen clusterin is a novel DC-SIGN ligand,” Journal of Immunology, vol. 187, pp. 5299–5309, 2011. View at: Google Scholar
  14. M. Sakakura, S. Oo-Puthinan, C. Moriyama et al., “Carbohydrate binding mechanism of the macrophage galactose-type C-type lectin 1 revealed by saturation transfer experiments,” Journal of Biological Chemistry, vol. 283, no. 48, pp. 33665–33673, 2008. View at: Publisher Site | Google Scholar
  15. N. M. Dahms and M. K. Hancock, “P-type lectins,” Biochimica et Biophysica Acta, vol. 1572, no. 2-3, pp. 317–340, 2002. View at: Publisher Site | Google Scholar
  16. X. Song, Y. Lasanajak, L. J. Olson et al., “Glycan microarray analysis of P-type lectins reveals distinct phosphomannose glycan recognition,” Journal of Biological Chemistry, vol. 284, no. 50, pp. 35201–35214, 2009. View at: Publisher Site | Google Scholar
  17. J. J. P. Kim, L. J. Olson, and N. M. Dahms, “Carbohydrate recognition by the mannose-6-phosphate receptors,” Current Opinion in Structural Biology, vol. 19, no. 5, pp. 534–542, 2009. View at: Publisher Site | Google Scholar
  18. J. Chen, S. Xiao, and Z. Yu, “F-type lectin involved in defense against bacterial infection in the pearl oyster (Pinctada martensii),” Fish and Shellfish Immunology, vol. 30, no. 2, pp. 750–754, 2011. View at: Publisher Site | Google Scholar
  19. H. J. Park, J. W. Kim, E. G. Kim et al., “Molecular cloning and expression analysis of two distinct F-type lectins from the rock bream, Oplegnathus fasciatus,” Developmental and Comparative Immunology, vol. 36, pp. 230–235, 2012. View at: Publisher Site | Google Scholar
  20. E. W. Odom and G. R. Vasta, “Characterization of a binary tandem domain F-type lectin from striped bass (Morone saxatilis),” Journal of Biological Chemistry, vol. 281, no. 3, pp. 1698–1713, 2006. View at: Publisher Site | Google Scholar
  21. T. Ogawa, M. Watanabe, T. Naganuma, and K. Muramoto, “Diversified carbohydrate-binding lectins from marine resources,” Journal of Amino Acids, vol. 2011, Article ID 838914, 20 pages, 2011. View at: Publisher Site | Google Scholar
  22. M. A. Bianchet, E. W. Odom, G. R. Vasta, and L. M. Amzel, “Structure and specificity of a binary tandem domain F-Lectin from striped bass (Morone saxatilis),” Journal of Molecular Biology, vol. 401, no. 2, pp. 239–252, 2010. View at: Publisher Site | Google Scholar
  23. M. K. O'Reilly and J. C. Paulson, “Siglecs as targets for therapy in immune-cell-mediated disease,” Trends in Pharmacological Sciences, vol. 30, no. 5, pp. 240–248, 2009. View at: Publisher Site | Google Scholar
  24. C. Jandus, H. U. Simon, and S. Von Gunten, “Targeting Siglecs-A novel pharmacological strategy for immuno- and glycotherapy,” Biochemical Pharmacology, vol. 82, no. 4, pp. 323–332, 2011. View at: Publisher Site | Google Scholar
  25. D. Sancho and C. Reis e Sousa, “Signaling by myeloid C-Type lectin receptors in immunity and homeostasis,” Annual Review of Immunology, vol. 30, pp. 491–529, 2012. View at: Publisher Site | Google Scholar
  26. T. K. Dam and C. Fred Brewer, “Lectins as pattern recognition molecules: the effects of epitope density in innate immunity,” Glycobiology, vol. 20, no. 3, Article ID cwp186, pp. 270–279, 2009. View at: Publisher Site | Google Scholar
  27. Y. van Kooyk, “C-type lectins on dendritic cells: key modulators for the induction of immune responses,” Biochemical Society Transactions, vol. 36, no. 6, pp. 1478–1481, 2008. View at: Publisher Site | Google Scholar
  28. W. I. Weis, M. E. Taylor, and K. Drickamer, “The C-type lectin superfamily in the immune system,” Immunological Reviews, vol. 163, pp. 19–34, 1998. View at: Publisher Site | Google Scholar
  29. D. C. Kilpatrick, “Animal lectins: a historical introduction and overview,” Biochimica et Biophysica Acta, vol. 1572, no. 2-3, pp. 187–197, 2002. View at: Publisher Site | Google Scholar
  30. R. S. Singh and H. H. Wang, “Timing of repeat thyroid fine-needle aspiration in the management of thyroid nodules,” Acta Cytologica, vol. 55, no. 6, pp. 544–548, 2011. View at: Publisher Site | Google Scholar
  31. A. Engering, T. B. H. Geijtenbeek, and Y. Van Kooyk, “Immune escape through C-type lectins on dendritic cells,” Trends in Immunology, vol. 23, no. 10, pp. 480–485, 2002. View at: Publisher Site | Google Scholar
  32. A. Engering, T. B. H. Geijtenbeek, S. J. Van Vliet et al., “The dendritic cell-specific adhesion receptor DC-SIGN internalizes antigen for presentation to T cells,” Journal of Immunology, vol. 168, no. 5, pp. 2118–2126, 2002. View at: Google Scholar
  33. G. D. Brown, J. Herre, D. L. Williams, J. A. Willment, A. S. J. Marshall, and S. Gordon, “Dectin-1 mediates the biological effects of β-glucans,” Journal of Experimental Medicine, vol. 197, no. 9, pp. 1119–1124, 2003. View at: Publisher Site | Google Scholar
  34. B. N. Gantner, R. M. Simmons, S. J. Canavera, S. Akira, and D. M. Underhill, “Collaborative induction of inflammatory responses by dectin-1 and toll-like receptor 2,” Journal of Experimental Medicine, vol. 197, no. 9, pp. 1107–1117, 2003. View at: Publisher Site | Google Scholar
  35. P. Chakraborty, D. Ghosh, and M. K. Basu, “Modulation of macrophage mannose receptor affects the uptake of virulent and avirulent Leishmania donovani promastigotes,” Journal of Parasitology, vol. 87, no. 5, pp. 1023–1027, 2001. View at: Google Scholar
  36. S. Oo-puthinan, K. Maenuma, M. Sakakura et al., “The amino acids involved in the distinct carbohydrate specificities between macrophage galactose-type C-type lectins 1 and 2 (CD301a and b) of mice,” Biochimica et Biophysica Acta, vol. 1780, no. 2, pp. 89–100, 2008. View at: Publisher Site | Google Scholar
  37. U. Švajger, M. Anderluh, M. Jeras, and N. Obermajer, “C-type lectin DC-SIGN: an adhesion, signalling and antigen-uptake molecule that guides dendritic cells in immunity,” Cellular Signalling, vol. 22, no. 10, pp. 1397–1405, 2010. View at: Publisher Site | Google Scholar
  38. D. H. Lloyd, J. Viac, D. Werling, C. A. Rème, and H. Gatto, “Role of sugars in surface microbe-host interactions and immune reaction modulation,” Veterinary Dermatology, vol. 18, no. 4, pp. 197–204, 2007. View at: Publisher Site | Google Scholar
  39. L. M. Kingeter and X. Lin, “C-type lectin receptor-induced NF-kappaB activation in innate immune and inflammatory responses,” Cellular & Molecular Immunology, vol. 9, pp. 105–112, 2012. View at: Google Scholar
  40. S. J. Van Vliet, J. J. García-Vallejo, and Y. Van Kooyk, “Dendritic cells and C-type lectin receptors: coupling innate to adaptive immune responses,” Immunology and Cell Biology, vol. 86, no. 7, pp. 580–587, 2008. View at: Publisher Site | Google Scholar
  41. M. J. Robinson, D. Sancho, E. C. Slack, S. LeibundGut-Landmann, and C. R. Sousa, “Myeloid C-type lectins in innate immunity,” Nature Immunology, vol. 7, no. 12, pp. 1258–1265, 2006. View at: Publisher Site | Google Scholar
  42. T. P. Dorlo, M. Balasegaram, J. H. Beijnen, and P. J. de Vries, “Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis,” Journal of Antimicrobial Chemotherapy, vol. 67, no. 11, pp. 2576–2597, 2012. View at: Publisher Site | Google Scholar
  43. J. Alvar, I. D. Velez, C. Bern et al., “Leishmaniasis worldwide and global estimates of its incidence,” PLoS One, vol. 7, no. 5, Article ID e35671, 2012. View at: Publisher Site | Google Scholar
  44. L. Beattie and P. M. Kaye, “Leishmania-host interactions: what has imaging taught us?” Cell Microbiol, vol. 13, pp. 1659–1667, 2011. View at: Google Scholar
  45. O. E. Akilov, R. E. Kasuboski, C. R. Carter, and M. A. McDowel, “The role of mannose receptor during experimental leishmaniasis,” Journal of Leukocyte Biology, vol. 81, no. 5, pp. 1188–1196, 2007. View at: Publisher Site | Google Scholar
  46. V. V. Garrido, L. R. Dulgerian, C. C. Stempin, and F. M. Cerban, “The increase in mannose receptor recycling favors arginase induction and Trypanosoma cruzi survival in macrophages,” International Journal of Biological Sciences, vol. 7, pp. 1257–1272, 2011. View at: Google Scholar
  47. M. L. Deschoolmeester, L. Martinez-Pomares, S. Gordon, and K. J. Else, “The mannose receptor binds Trichuris muris excretory/secretory proteins but is not essential for protective immunity,” Immunology, vol. 126, no. 2, pp. 246–255, 2009. View at: Publisher Site | Google Scholar
  48. N. Basu, R. Sett, and P. K. Das, “Down-regulation of mannose receptors on macrophages after infection with Leishmania donovani,” Biochemical Journal, vol. 277, no. 2, pp. 451–456, 1991. View at: Google Scholar
  49. M. E. Wilson and R. D. Pearson, “Evidence that Leishmania donovani utilizes a mannose receptor on human mononuclear phagocytes to establish intracellular parasitism,” Journal of Immunology, vol. 136, no. 12, pp. 4681–4688, 1986. View at: Google Scholar
  50. M. Colmenares, A. Puig-Kröger, O. M. Pello, A. L. Corbí, and L. Rivas, “Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor for Leishmania amastigotes,” Journal of Biological Chemistry, vol. 277, no. 39, pp. 36766–36769, 2002. View at: Publisher Site | Google Scholar
  51. M. Colmenares, A. L. Corbí, S. J. Turco, and L. Rivas, “The dendritic Cell receptor DC-sign discriminates among species and life cycle forms of Leishmania,” Journal of Immunology, vol. 172, no. 2, pp. 1186–1190, 2004. View at: Google Scholar
  52. M. D. N. C. Soeiro, M. M. Paiva, H. S. Barbosa, M. D. N. S. L. Meirelles, and T. C. Araújo-Jorge, “A cardiomyocyte mannose receptor system is involved in Trypanosoma cruzi invasion and is down-modulated after infection,” Cell Structure and Function, vol. 24, no. 3, pp. 139–149, 1999. View at: Publisher Site | Google Scholar
  53. G. Raes, L. Brys, B. K. Dahal et al., “Macrophage galactose-type C-type lectins as novel markers for alternatively activated macrophages elicited by parasitic infections and allergic airway inflammation,” Journal of Leukocyte Biology, vol. 77, no. 3, pp. 321–327, 2005. View at: Publisher Site | Google Scholar
  54. S. J. van Vliet, E. van Liempt, E. Saeland et al., “Carbohydrate profiling reveals a distinctive role for the C-type lectin MGL in the recognition of helminth parasites and tumor antigens by dendritic cells,” International Immunology, vol. 17, no. 5, pp. 661–669, 2005. View at: Publisher Site | Google Scholar
  55. E. van Liempt, S. J. van Vliet, A. Engering et al., “Schistosoma mansoni soluble egg antigens are internalized by human dendritic cells through multiple C-type lectins and suppress TLR-induced dendritic cell activation,” Molecular Immunology, vol. 44, no. 10, pp. 2605–2615, 2007. View at: Publisher Site | Google Scholar
  56. I. van Die, S. J. van Vliet, A. K. Nyame et al., “The dendritic cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan antigen Lewis x,” Glycobiology, vol. 13, no. 6, pp. 471–478, 2003. View at: Publisher Site | Google Scholar
  57. S. Meyer, B. Tefsen, A. Imberty, R. Geyer, and I. van die, “The C-type lectin L-SIGN differentially recognizes glycan antigens on egg glycosphingolipids and soluble egg glycoproteins from Schistosoma mansoni,” Glycobiology, vol. 17, no. 10, pp. 1104–1119, 2007. View at: Publisher Site | Google Scholar
  58. M. Ritter, O. Gross, S. Kays et al., “Schistosoma mansoni triggers Dectin-2, which activates the Nlrp3 inflammasome and alters adaptive immune responses,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 47, pp. 20459–20464, 2010. View at: Publisher Site | Google Scholar
  59. R. A. Paveley, S. A. Aynsley, J. D. Turner et al., “The Mannose Receptor (CD206) is an important pattern recognition receptor (PRR) in the detection of the infective stage of the helminth Schistosoma mansoni and modulates IFNgamma production,” International Journal for Parasitology, vol. 41, pp. 1335–1345, 2011. View at: Google Scholar
  60. C. A. Terrazas, F. Sanchez-Munoz, A. M. Mejia-Dominguez et al., “Cestode antigens induce a tolerogenic-like phenotype and inhibit LPS inflammatory responses in human dendritic cells,” International Journal of Biological Sciences, vol. 7, pp. 1391–1400, 2011. View at: Google Scholar
  61. R. Garg, N. Trudel, and M. J. Tremblay, “Consequences of the natural propensity of Leishmania and HIV-1 to target dendritic cells,” Trends in Parasitology, vol. 23, no. 7, pp. 317–324, 2007. View at: Publisher Site | Google Scholar
  62. C. A. Terrazas, E. Huitron, A. Vazquez et al., “MIF synergizes with Trypanosoma cruzi antigens to promote efficient dendritic cell maturation and IL-12 production via p38 MAPK,” International Journal of Biological Sciences, vol. 7, pp. 1298–1310, 2011. View at: Google Scholar
  63. M. M. Rodrigues, A. C. Oliveira, and M. Bellio, “The immune response to Trypanosoma cruzi: role of toll-like receptors and perspectives for vaccine development,” Journal of Parasitology Research, vol. 2012, Article ID 507874, 12 pages, 2012. View at: Publisher Site | Google Scholar
  64. M. A. Campos and R. T. Gazzinelli, “Trypanosoma cruzi and its components as exogenous mediators of inflammation recognized through Toll-like receptors,” Mediators of Inflammation, vol. 13, no. 3, pp. 139–143, 2004. View at: Publisher Site | Google Scholar
  65. C. Ropert, L. R. P. Ferreira, M. A. S. Campos et al., “Macrophage signaling by glycosylphosphatidylinositol-anchored mucin-like glycoproteins derived from Trypanosoma cruzi trypomastigotes,” Microbes and Infection, vol. 4, no. 9, pp. 1015–1025, 2002. View at: Publisher Site | Google Scholar
  66. P. E. A. Souza, M. O. C. Rocha, C. A. S. Menezes et al., “Trypanosoma cruzi infection induces differential modulation of costimulatory molecules and cytokines by monocytes and T cells from patients with indeterminate and cardiac Chagas' disease,” Infection and Immunity, vol. 75, no. 4, pp. 1886–1894, 2007. View at: Publisher Site | Google Scholar
  67. T. Jacobs, H. Erdmann, and B. Fleischer, “Molecular interaction of Siglecs (sialic acid-binding Ig-like lectins) with sialylated ligands on Trypanosoma cruzi,” European Journal of Cell Biology, vol. 89, no. 1, pp. 113–116, 2010. View at: Publisher Site | Google Scholar
  68. A. Acosta-Serrano, I. C. Almeida, L. H. Freitas-Junior, N. Yoshida, and S. Schenkman, “The mucin-like glycoprotein super-family of Trypanosoma cruzi: structure and biological roles,” Molecular and Biochemical Parasitology, vol. 114, no. 2, pp. 143–150, 2001. View at: Publisher Site | Google Scholar
  69. A. C. Oliveira, J. R. Peixoto, L. B. De Arrada et al., “Expression of functional TLR4 confers proinflammatory responsiveness to Trypanosoma cruzi glycoinositolphospholipids and higher resistance to infection with T. cruzi,” Journal of Immunology, vol. 173, no. 9, pp. 5688–5696, 2004. View at: Google Scholar
  70. A. Beschin, L. Brys, S. Magez, M. Radwanska, and P. De Baetselier, “Trypanosoma brucei infection elicits nitric oxide-dependent and nitric oxide-independent suppressive mechanisms,” Journal of Leukocyte Biology, vol. 63, no. 4, pp. 429–439, 1998. View at: Google Scholar
  71. A. Atrih, J. M. Richardson, A. R. Prescott, and M. A. J. Ferguson, “Trypanosoma brucei glycoproteins contain novel giant poly-N- acetyllactosamine carbohydrate chains,” Journal of Biological Chemistry, vol. 280, no. 2, pp. 865–871, 2005. View at: Publisher Site | Google Scholar
  72. M. D. Urbaniak, D. C. Turnock, and M. A. J. Ferguson, “Galactose starvation in a bloodstream form Trypanosoma brucei UDP-glucose 4′-epimerase conditional null mutant,” Eukaryotic Cell, vol. 5, no. 11, pp. 1906–1913, 2006. View at: Publisher Site | Google Scholar
  73. Y. Kumamoto, N. Higashi, K. Denda-Nagai et al., “Identification of sialoadhesin as a dominant lymph node counter-receptor for mouse macrophage galactose-type C-type lectin,” Journal of Biological Chemistry, vol. 279, no. 47, pp. 49274–49280, 2004. View at: Publisher Site | Google Scholar
  74. M. Tsuiji, M. Fujimori, Y. Ohashi et al., “Molecular cloning and characterization of a novel mouse macrophage C-type lectin, mMGL2, which has a distinct carbohydrate specificity from mMGL1,” Journal of Biological Chemistry, vol. 277, no. 32, pp. 28892–28901, 2002. View at: Google Scholar
  75. Y. Kumamoto, K. Denda-Nagai, S. Aida, N. Higashi, and T. Irimura, “MGL2+ dermal dendritic cells are sufficient to initiate contact hypersensitivity in vivo,” PLoS One, vol. 4, no. 5, Article ID e5619, 2009. View at: Publisher Site | Google Scholar
  76. S. J. van Vliet, C. A. Aarnoudse, V. C. M. Broks-van den Nerg, M. Boks, T. B. H. Geijtenbeek, and Y. van Kooyk, “MGL-mediated internalization and antigen presentation by dendritic cells: a role for tyrosine-5,” European Journal of Immunology, vol. 37, no. 8, pp. 2075–2081, 2007. View at: Publisher Site | Google Scholar
  77. S. K. Singh, I. Streng-Ouwehand, M. Litjens et al., “Characterization of murine MGL1 and MGL2 C-type lectins: distinct glycan specificities and tumor binding properties,” Molecular Immunology, vol. 46, no. 6, pp. 1240–1249, 2009. View at: Publisher Site | Google Scholar
  78. S. Gaherwal and M. M. Prakash, “Lymphocyte migration inhibition response in Trichuris muris infected and vaccinated mice,” Iranian Journal of Parasitology, vol. 6, no. 1, pp. 34–40, 2011. View at: Google Scholar
  79. C. M. W. van Stijn, S. Meyer, M. van den Broek et al., “Schistosoma mansoni worm glycolipids induce an inflammatory phenotype in human dendritic cells by cooperation of TLR4 and DC-SIGN,” Molecular Immunology, vol. 47, no. 7-8, pp. 1544–1552, 2010. View at: Publisher Site | Google Scholar
  80. M. H. J. Meevissen, M. Yazdanbakhsh, and C. H. Hokke, “Schistosoma mansoni egg glycoproteins and C-type lectins of host immune cells: molecular partners that shape immune responses,” Experimental Parasitology, vol. 132, no. 1, pp. 14–21, 2011. View at: Publisher Site | Google Scholar
  81. A. A. Bashirova, T. B. H. Geijtenbeek, G. C. F. Van Duijnhoven et al., “A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection,” Journal of Experimental Medicine, vol. 193, no. 6, pp. 671–678, 2001. View at: Publisher Site | Google Scholar
  82. H. J. Choi, W. S. Choi, J. Y. Park et al., “SIGN-R1, a C-type lectin, binds to Bip/GRP78 and this interaction mediates the regurgitation of T-cell-independent type 2 antigen dextran through the endoplasmic reticulum,” Immunobiology, vol. 216, no. 4, pp. 437–446, 2011. View at: Publisher Site | Google Scholar
  83. K. Takahara, S. Tokieda, K. Nagaoka, and K. Inaba, “Efficient capture of Candida albicans and zymosan by SIGNR1 augments TLR2-dependent TNF-α production,” International Immunology, vol. 24, no. 2, pp. 89–96, 2012. View at: Publisher Site | Google Scholar
  84. S. Saijo and Y. Iwakura, “Dectin-1 and Dectin-2 in innate immunity against fungi,” International Immunology, vol. 23, no. 8, pp. 467–472, 2011. View at: Publisher Site | Google Scholar
  85. J. Sainz, C. B. Lupiáñez, J. Segura-Catena et al., “Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary aspergillosis infection,” PLoS One, vol. 7, no. 2, Article ID e32273, 2012. View at: Publisher Site | Google Scholar
  86. L. I. Terrazas, R. Bojalil, T. Govezensky, and C. Larralde, “Shift from an early protective TH1-type immune response to a late permissive TH2-type response in murine cysticercosis (Taenia crassiceps),” Journal of Parasitology, vol. 84, no. 1, pp. 74–81, 1998. View at: Publisher Site | Google Scholar
  87. L. Gómez-García, L. M. López-Marín, R. Saavedra, J. L. Reyes, M. Rodríguez-Sosa, and L. I. Terrazas, “Intact glycans from cestode antigens are involved in innate activation of myeloid suppressor cells,” Parasite Immunology, vol. 27, no. 10-11, pp. 395–405, 2005. View at: Publisher Site | Google Scholar
  88. J. L. Reyes, C. A. Terrazas, L. Vera-Arias, and L. I. Terrazas, “Differential response of antigen presenting cells from susceptible and resistant strains of mice to Taenia crassiceps infection,” Infection, Genetics and Evolution, vol. 9, no. 6, pp. 1115–1127, 2009. View at: Publisher Site | Google Scholar

Copyright © 2013 Alicia Vázquez-Mendoza et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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