title: Toll-Like Receptor-4 Dependent Small Intestinal Immune Responses Following Murine Arcobacter Butzleri Infection.
abstract: Sporadic cases of gastroenteritis have been attributed to Arcobacter butzleri infection, but information about the underlying immunopathological mechanisms is scarce. We have recently shown that experimental A. butzleri infection induces intestinal, extraintestinal and systemic immune responses in gnotobiotic IL-10(-/-) mice. The aim of the present study was to investigate the immunopathological role of Toll-like Receptor-4, the receptor for lipopolysaccharide and lipooligosaccharide of Gram-negative bacteria, during murine A. butzleri infection. To address this, gnotobiotic IL-10(-/-) mice lacking TLR-4 were generated by broad-spectrum antibiotic treatment and perorally infected with two different A. butzleri strains isolated from a patient (CCUG 30485) or fresh chicken meat (C1), respectively. Bacteria of either strain stably colonized the ilea of mice irrespective of their genotype at days 6 and 16 postinfection. As compared to IL-10(-/-) control animals, TLR-4(-/-) IL-10(-/-) mice were protected from A. butzleri-induced ileal apoptosis, from ileal influx of adaptive immune cells including T lymphocytes, regulatory T-cells and B lymphocytes, and from increased ileal IFN-γ secretion. Given that TLR-4-signaling is essential for A. butzleri-induced intestinal inflammation, we conclude that bacterial lipooligosaccharide or lipopolysaccharide compounds aggravate intestinal inflammation and may thus represent major virulence factors of Arcobacter. Future studies need to further unravel the molecular mechanisms of TLR-4-mediated A. butzleri-host interactions.
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
authors.affiliation: Institute of Food Hygiene, Freie Universität Berlin , Berlin, Germany.
authors.forename: Gül
authors.initials: G
authors.lastname: Karadas
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Ulf B
authors.initials: UB
authors.lastname: Göbel
authors.affiliation: Institute of Food Hygiene, Freie Universität Berlin , Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Alter
authors.affiliation: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bereswill
authors.affiliation: Institute of Food Hygiene, Freie Universität Berlin , Berlin, Germany.
authors.forename: Greta
authors.initials: G
authors.lastname: Gölz
keywords: Arcobacter butzleri; Toll-like Receptor-4; apoptosis; host-pathogen interactions; innate immunity; lipooligosaccharide; lipopolysaccharide; pro-inflammatory immune responses; small intestine; spleen