Leishmania mexicana infection induces antibody responses to parasite surface glycolipids that can induce IL-10 and suppress IL-12 from macrophages (37.25)

Abstract

Abstract Chronic disease of mice caused by the protozoan parasite Leishmania mexicana requires IL-10 and FcγRIII. Immune complexes consisting of IgG bound to the surface of Leishmania amastigotes can induce IL-10 and suppress IL-12 production from macrophages. However, the targets of these antibodies and the kinetics of their production are not known. Several groups have attempted, without success, to identify surface proteins on the amastigote form of the parasite to which IgG can bind. Using ELISA and thin layer chromatography (TLC) immunoblot methods we now show that parasite glycoinositol phospholipids (GIPLs) of L. mexicana are recognized by IgG1 by 6 weeks of infection with a rapid increase between 14-16 wks, consistent with the timing of chronic disease in C57BL/6 mice vs. healing in FcγRIII KO mice. We found that a single prominent spot on TLC is recognized by mouse serum of infected mice and that the glycolipid has a glycosyl phosphatidylinositol (GPI) structure as assessed by GPI-PLC and GPI-PLD susceptibility. Alpha-mannosidase treatment changed the mobility of the recognized glycolipid, indicating that a branched mannose occurs in the structure, but is not required for IgG binding. Further characterization of the target glycolipids will have important implications for vaccine development as well as elucidating the poorly understood role of glycolipids in immunology. Funded by VA Merit, the University of Pennsylvania, and NIH R01-AI081717.