Exogenous Control of the Expression of Group I CD1 Molecules Competent for Presentation of Microbial Nonpeptide Antigens to Human T Lymphocytes

Table 5

Influence exerted by infectious agents or microorganism products on group 1 CD1 antigen expression.

Infectious Agent	Agent	CD1^a	ED^b	Ref.^c	Observations
Bacteria	Helicobacter pilori E. coli	D	ED-1	[227]	In vitro exposure to paraformaldehyde-fixed bacteria. IL-10 independent.
	Helicobacter pilori (in vivo)	U	IvDC	[228]	In vivo detected by antral biopsies (lamina propria): increased CD1a and CD1b in infected children with respect to normal subjects. Expression of local immune responses.
	Propionibacterium acnes	U	ED-2	[229]	Heat-killed bacteria added on day 6 to iDCs of pts with acne vulgaris.
	Various	U	OED	[230]	Increased CD1a expression in in vitro generation of mDCs from MS pts with bacterial infections versus MS pts without infections.
Chlamydia	Chlamydia trachomatis	U	IvDC	[231]	Myeloid DCs collected from cervical mucosa of chlamydia-infected woman show myeloid DCs with increased CD1a expression with respect to that of healthy women.
Mycoplasma	Mycoplasma present in cell culture supernatant	D	ED-1	[232]	If mycoplasma is removed, culture supernatants are no more able to down-regulate CD1a.
Protozoa	Leishmania donovani	D	ED-1	[233]	L. donovani infection in vitro impairs induction of CD1a/b/c expression in terms of gene transcript and protein.
	Leishmania amazonensis	D	ED-1; ED-4	[234]	Leishmania or soluble Leishmania antigen inhibited CD1a expression, but did not prevent further DC maturation toward CD83^+ mDCs.
	Leishmania donovani and Leishmania major	D	OED	[235]	In vitro G4-induced iDCs were infected with L. donovani or L. major on day 7 and tested for CD1a/b/c/d expression 8 h later. Down-regulation of mainly Group I CD1 molecules at the transcriptional (qRT-PCR) and surface expression levels was detected.
	Toxoplasma gondii	NC	OED	[236]	In vitro infection of untreated MOs with T. gondii does not induce CD1a.
Helminthes	Necator Americanus	D	OED	[237]	In vitro G4-induced CD1a in mDCs is lower when MOs were obtained from infected pts versus normal donors.
	Echinococcus granulosus	D	ED-1; ED-4	[238, 239]	Hydatid cyst components (AgB- and SHF) down-regulate CD1a and further prevent IL-12 production, increasing IL-10 release.
Viruses (for HIV& HTLV-I see text)	Human Herpes Virus-8 (alive or UV-inactivated)	D	ED-1	[240]	Reduced mDC activity and sixfold reduction in IL-12 (p70) production with consequent impairment of T-cell-mediated responses.
	Cytomegalovirus	D	ED-1	[241]	CD1a assay at day 7, before adding LPS (to evaluate iDC CD1a expression). Down-regulation of CD1a occurs also with UV-inactivated virus. Moreover, HCMV-infected mDCs were unable to induce a T-cell response, in line with the immunodepressive effects of HCMV infection.
Micro-Organism products
Bordetella pertussis	Pertussis toxin	D	ED-1	[242]	Selective suppression of CD1a (mRNA and protein) but not of CD1b and CD1c. LPS-induced mDCs are functionally normal.
Candida albicans	Supernatant	D	ED-1	[243]	C. albicans supernatants contain a glycoprotein termed “Secretory IL-12 Inhibitory Factor”, able to down-regulate CD1a expression and IL-12 production by iDCs and DCs.
Dengue	Dengue-2 (live attenuated vaccines)	U	ED-2	[244]	DC maturation step 2 was attained with live attenuate vaccine LAV2 or DEN2 without adding LPS. Heat-inactivated virus was used as a negative control for virus infection. CD1a assay was performed after incubation at 32°C for 48 h.
Malaria	Hemozoin (malaria pigment)	D	ED-1; ED-4	[245]	Mechanism: increased PPARγ expression (qRT-PCR) following hemozoin-induced activation in MOs.
	Atypical Membrane Antigen-1 (AMA-1)	U	ED-4	[246]	mDCs of P. vivax infected pts show lower CD1a expression than that of mDCs developed in vitro from MOs of noninfected controls. In vitro exposure to AMA-1 increases CD1a levels in mDCs developed in vitro from MOs of infected donors.
Mycotoxins	T-2 toxin	D	ED-1	[247]	Strong inhibition.
Staphylococcus aureus	Staphylococcus superantigen	U	IvDC	[248]	CD1a^+ cell number in the epidermis was significantly higher in the lesional skin with respect to that in non-lesional skin from atopic dermatitis pts or to that in the skin from normal donors.
Various bacteria	LPS	D	ED-1	[249]	LPS (from Salmonella) was added to MOs+G4 culture on day 0 instead of on day 5–9, as usually used for inducing iDC maturation to mDCs. Mechanism: in part by induction of IL-10, and mostly by MAPKp38 activation followed by ERK and NF-kB inactivation.

^aEvaluation of CD1a expression if not otherwise specified: U: upregulation; D: down-regulation.
^bExperimental design code (see Figure 2).
^cReference number.