Receptors and recognition mechanisms of Leishmania species.
This paper examines briefly receptors and recognition mechanisms involved in binding Leishmania parasites to the lumen of the sandfly gut and to cells of the vertebrate host's mononuclear phagocyte system. In particular, work carried out in our laboratory on the relative roles of the macrophage plasma membrane receptor (CR3) for the cleaved third complement component (iC3b) and the mannosyl/fucosyl receptor (MFR) in binding, ingestion and respiratory burst (RB) response elicited by promastigotes versus amastigotes of L. donovani, is discussed. In the absence of serum, soluble inhibitors (e.g. mannan) of the MFR cause a dose-dependent reduction in promastigote binding to murine resident peritoneal macrophages and in the proportion of bound parasites eliciting a RB response. For amastigotes, no consistent reduction in binding in the presence of mannan is observed but the proportion of parasites eliciting a RB is reduced. Serum-independent binding of promastigotes, which are good activators of the alternative complement pathway, is also inhibited by the anti-CR3 monoclonal antibody M1/70, by Fab anti-C3, and by an inhibitor of C3 fixation, sodium salicyl hydroxamate. With amastigotes, which are poor activators of the alternative pathway, a lesser effect is observed. These results provide strong evidence that cleaved macrophage-derived C3 (iC3b) mediates promastigote binding to CR3. Modulation experiments in which either CR3 or MFR are rendered inaccessible demonstrate that both receptors must be present on the segment of macrophage membrane with which the promastigote makes contact to mediate binding and ingestion. These receptor interactions may be important determinants of the infectivity and survival of Leishmania parasites in the vertebrate host.
D000818:Animals; D001667:Binding, Competitive; D002462:Cell Membrane; D005643:Fucose / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type; D007891:Leishmania / Q000472:pathogenicity*; D008024:Ligands; D016177:Macrophage-1 Antigen; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D008358:Mannose / Q000378:metabolism; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009895:Opsonin Proteins; D010586:Phagocytes / Q000469:parasitology*; D011576:Psychodidae / Q000469:parasitology*; D011956:Receptors, Cell Surface; D011951:Receptors, Complement / Q000502:physiology; D011971:Receptors, Immunologic / Q000502:physiology; D014774:Virulence
D037181:Lectins, C-Type; D008024:Ligands; D016177:Macrophage-1 Antigen; D000090323:Mannose Receptor; D037241:Mannose-Binding Lectins; D009895:Opsonin Proteins; D011956:Receptors, Cell Surface; D011951:Receptors, Complement; D011971:Receptors, Immunologic; D005643:Fucose; D008358:Mannose