Chapter 4 - Anti-Gal Interaction With Trypanosoma, Leishmania, and Plasmodium Parasites

Abstract

The natural anti-Gal antibody binds to several protozoan parasites, including Trypanosoma, Leishmania, and Plasmodium. The binding is to α-gal-like epitopes presented by these parasites mostly on glycoinositol phospholipids and glycoproteins. These epitopes further stimulate the immune system of infected individuals to produce anti-Gal at elevated titers. In vitro studies with sera from infected patients and in vivo studies in GT-KO mice producing anti-Gal demonstrated complement-dependent and independent lysis and neutralization of Trypanosoma and Plasmodium parasites. These observations suggest that anti-Gal may con­tribute to natural protection against infections by these parasites. The high rates of infections suggest, however, that in a substantial proportion of populations in endemic regions, protective activity of the natural anti-Gal antibody is insufficient. Thus, significant numbers of infecting parasites succeed in evading the antibody by invading RBC or nucleated cells where they are protected from anti-Gal. Moreover, shedding of Trypanosoma cell membranes in the chronic phase of Chagas’ disease may cause anti-Gal-mediated autoimmune-like phe­nomena that could be lethal, in particular, because of heart failure. In view of these consid­erations, it may be of interest to determine whether constant elevation of anti-Gal activity in individuals in endemic regions may contribute to protection against such infections. It is not clear whether immunization with vaccines inducing increased production of anti-Gal may be helpful because anti-Gal activity usually returns to the preimmunization level, within few months post immunization. It may be possible that providing nonpathogenic bacteria (e.g., as food supplement) that elevate anti-Gal production, and which become an integral part of the microbiome, will result in continuous increase in anti-Gal titers to levels that enable effective destruction of invading parasites, thus increasing protection against such infections.