Iron Homeostasis and Trypanosoma brucei Associated Immunopathogenicity Development: A Battle/Quest for Iron

Figure 2

Iron modulation and pathogenicity development during T. brucei infection. Trypanosomes are equipped with different molecules to acquire iron from the mammalian host, namely, via their ESAG6/7 Tf-R (involved in Tf uptake), GADPH Lf-R (involved in Lf uptake), and the HbHpR (involved in heme/hemoglobin uptake). Parasites release molecules like the GPI-anchor or CpG-DNA to modulate/activate the host MYPS for their own benefit (1). Most of these molecules released by death or phagocytosed parasites trigger the release of proinflammatory molecules by M1-type myeloid cells, including Gal-3 and MIF (2). Both molecules stimulate iron-retention by inducing expression of HO-1, DMT-1, and FHC and by decreasing expression of FPN-1 within M1-type MYPS cells (3). Gal-3 by stimulating erythrophagocytosis (4) and MIF by suppressing erythropoiesis (5) contribute to anemia development. Due to their antiapoptotic effect, Gal-3 and MIF favor the persistence of the pathogenic M1-type MYPS. Moreover, MIF contributes to the recruitment of other pathogenic myeloid cells such as monocytes and neutrophils and further fuels the development of liver injury (6). GPI: glycosylphosphatidylinositol; Gal-3: galectin-3; MIF: macrophage migration inhibitory factor; Tf: transferrin; Tf-R: transferrin-receptor; Lf: lactoferrin; Lf-R: lactoferrin-receptor; HO-1: heme oxygenase 1; DMT-1: Divalent metal ion transporter 1; FPN-1: ferroportin-1; ESAG6/7 Tf-R: expression-site-associated genes (ESAG) 6 and 7; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; HpHbR: haptoglobin-hemoglobin receptor; MYPS: myeloid phagocyte system. Figure adapted from [20].