Pattern Recognition Receptor Engagement is Necessary for Leishmania Inhibition of Macrophage Phagosome Maturation. (133.35)

Abstract

Abstract Leishmania species are obligate intracellular parasites that reside primarily within macrophages (MP), cells whose primary function is to eliminate invading micro-organisms. Leishmania parasites avoid MP destruction by delaying the normal phagosome maturation pathway, allowing the parasites time to develop into a more resistant life cycle form. Leishmania entry into host cells is receptor mediated. These parasites are able to engage numerous cell surface receptors including, mannose receptor (MR), Toll-like receptors (TLR), Fc receptors (FcR), and complement receptor 3 (CR3). Assessing EEA-1 (early marker) and LAMP-1 (late marker) by confocal microscopy, we investigated the role that pattern recognition receptor engagement has on the maturation of Leishmania-containing phagosomes. CR3, TLR-2, and FcR were necessary for the 5 hour phagosome maturation delay characteristic of Leishmania infection. MR deficient macrophages exhibited a unique phagosome maturation pattern not observed for TLR-2, CR3 and FcR deficient MP. Progression to the late phagosome occured at one-hour similar to phagosomes in TLR-2, CR3 and FcR deficient MP; however, at 4 hours phagosomes returned to the early state as marked by EEA1 with late maturation occurring again at 5 hours. Interestingly, pattern recognition receptor deficiency resulted in faster phagosome maturation but had no influence on parasite entry.