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Figure 2: The role of lipopeptidophosphoglycan (LPPG) in the immune response to Entamoeba histolytica. During E. histolytica infection, amebic enzymes and enzymes and reactive oxygen species from neutrophils cause tissue damage. LPPG released from lysed trophozoites is recognized through TLR2 and TLR4/CD14 and induces the production of IL-8, IL-10, IL-12p40, and TNF-alpha by monocytes [85, 96]. Macrophages and dendritic cells internalize LPPG into LAMP-1+ endosomes, and LPPG-activated dendritic cells have increased expression of costimulatory molecules CD80, CD86, and CD40 and produce TNF-alpha, IL-8, and IL-12 [97]. NKT cells are also activated by LPPG, and this depends on the presence of CD1d on dendritic cells and simultaneous TLR2 and TLR6 signaling [58]. Anti-LPPG antibodies have been described in humans and in animal models [4753]. The mechanism that leads to the production of these antibodies has not been determined, but it is probably influenced by the innate signaling of LPPG on dendritic cells and B cells.