title: TNFα-mediated liver destruction by Kupffer cells and Ly6Chi monocytes during Entamoeba histolytica infection.
abstract: Amebic liver abscess (ALA) is a focal destruction of liver tissue due to infection by the protozoan parasite Entamoeba histolytica (E. histolytica). Host tissue damage is attributed mainly to parasite pathogenicity factors, but massive early accumulation of mononuclear cells, including neutrophils, inflammatory monocytes and macrophages, at the site of infection raises the question of whether these cells also contribute to tissue damage. Using highly selective depletion strategies and cell-specific knockout mice, the relative contribution of innate immune cell populations to liver destruction during amebic infection was investigated. Neutrophils were not required for amebic infection nor did they appear to be substantially involved in tissue damage. In contrast, Kupffer cells and inflammatory monocytes contributed substantially to liver destruction during ALA, and tissue damage was mediated primarily by TNFα. These data indicate that besides direct antiparasitic drugs, modulating innate immune responses may potentially be beneficial in limiting ALA pathogenesis.
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Helk
authors.forename: Hannah
authors.initials: H
authors.lastname: Bernin
authors.forename: Thomas
authors.initials: T
authors.lastname: Ernst
authors.forename: Harald
authors.initials: H
authors.lastname: Ittrich
authors.forename: Thomas
authors.initials: T
authors.lastname: Jacobs
authors.forename: Joerg
authors.initials: J
authors.lastname: Heeren
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.forename: Egbert
authors.initials: E
authors.lastname: Tannich
authors.forename: Hannelore
authors.initials: H
authors.lastname: Lotter
mesh_terms: D000818:Animals; D000950:Antigens, Ly; D004748:Entamoeba histolytica / Q000276:immunology / Q000472:pathogenicity; D004749:Entamoebiasis / Q000276:immunology* / Q000473:pathology*; D007113:Immunity, Innate; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007728:Kupffer Cells / Q000276:immunology* / Q000378:metabolism; D008099:Liver / Q000276:immunology / Q000473:pathology; D008101:Liver Abscess, Amebic / Q000276:immunology / Q000469:parasitology / Q000473:pathology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology* / Q000378:metabolism; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D000950:Antigens, Ly; C494192:Ly-6C antigen, mouse; D014409:Tumor Necrosis Factor-alpha; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse