Immune processes underlying ALA formation and regeneration
Stefan Hoenow, Marie Groneberg, Claudia Marggraff
Human amebiasis results from intestinal infections with the protozoan parasite Entamoeba histolytica (E. histolytica). The two major clinical symptoms that derive from the infections, the amebic colitis and the amebic liver abscess (ALA), represent major health problems in subtropical and tropical areas as well as in travellers. The parasite usually asymptomatically colonizes the bowel system, but occasionally it invades the mucosa and spreads via the blood stream into other organs, mainly in the liver. To investigate immunological backgrounds for the development of ALA, we have established a mouse model that resembles the human disease in terms of a comparable pathology and a similar sex distribution. Using selective depletion strategies and various knockout mutant mice, we were able to show that innate immune cells like the inflammatory Ly6Chi monocytes, but also liver resident Kupffer cells substantially contribute to the liver destruction via production of TNFα. IL-23 further contributes to immunopathology of ALA by stabilizing IL-17 production and CCL2 expression. On the other hand, tissue repair is initiated by the presence of anti-inflammatory Ly6Clo monocytes in the liver that produce IL-13 and further develop into alternative activated M2 macrophages expressing Arginase 1.
SFB841, " Leberentzündung: Infektion, Immunregulation und Konsequenzen" Project A2