The Role of Lipopeptidophosphoglycan in the Immune Response toEntamoeba histolytica

Abstract

The sensing of Pathogen Associated Molecular Patterns (PAMPs) by innate immune receptors, such as Toll-like receptors (TLRs), is the first step in the inflammatory response to pathogens. Entamoeba histolytica, the etiological agent of amebiasis, has a surface molecule with the characteristics of a PAMP. This molecule, which was termed lipopeptidophosphoglycan (LPPG), is recognized through TLR2 and TLR4 and leads to the release of cytokines from human monocytes, macrophages, and dendritic cells; LPPG-activated dendritic cells have increased expression of costimulatory molecules. LPPG activates NKT cells in a CD1d-dependent manner, and this interaction limits amebic liver abscess development. LPPG also induces antibody production, and anti-LPPG antibodies prevent disease development in animal models of amebiasis. Because LPPG is recognized by both the innate and the adaptive immune system (it is a “Pamptigen”), it may be a good candidate to develop a vaccine against E. histolytica infection and an effective adjuvant.

Detection of Entamoeba histolytica in experimentally induced amoebic liver abscess: comparison of three staining methods

“…In addition, other factors such as oxygen reduction ability, complement resistant, ROS and NOS scavenger capacity and immune evasion of the parasites also contribute to the parasites survival. Once the parasites are able to adapt to the environment in the liver, inflammation will be stimulated and followed by extensive tissue destruction [8,15,16] .…”

Molecular Basis of Pathogenesis in Amoebiasis

“…LPPG is also thought to initiate inflammatory and immune response in animal and in patients [42•, 43]. EhLPPG can recognize TLR-2 and TLR-4 on the surface of macrophage and dendritic cells stimulating the expression of cytokines and co-stimulatory molecules [43,44]. It mediates pro-inflammatory response after it enters the intestinal barrier [45].…”

Cell-Surface Molecules as Virulence Determinants in Entamoeba histolytica

“…A role for LPPG in the induction of host immune responses has been deduced from the following observations: Reduction of surface PPG (by interference with the expression of GPI-biosynthetic enzyme) provokes a drastic decrease in trophozoite survival in the presence of complement, and these parasites are avirulent in the hamster ALA model [ 76 ]. LPPG released from lysed trophozoites is recognized through toll-like receptors TLR2 and TLR4/CD14 and induces the production of interleukins IL-8, IL-10, IL-12p40, and TNF by monocytes ( [ 77 ] and references therein). Finally, LPPG is implicated in the protection against invasive amebiasis and specifi c activation of natural killer (NK) T cells by LPPG conferred signifi cant protection [ 78 ].…”