title: Toll-Like Receptor-4 is Essential for Arcobacter Butzleri-Induced Colonic and Systemic Immune Responses in Gnotobiotic IL-10(-/-) Mice.
abstract: Arcobacter butzleri causes sporadic cases of gastroenteritis, but the underlying immunopathological mechanisms of infection are unknown. We have recently demonstrated that A. butzleri-infected gnotobiotic IL-10(-/-) mice were clinically unaffected but exhibited intestinal and systemic inflammatory immune responses. For the first time, we here investigated the role of Toll-like receptor (TLR)-4, the main receptor for lipopolysaccharide and lipooligosaccharide of Gram-negative bacteria, in murine arcobacteriosis. Gnotobiotic TLR-4/IL-10-double deficient (TLR-4(-/-) IL-10(-/-)) and IL-10(-/-) control mice generated by broad-spectrum antibiotics were perorally infected with A. butzleri. Until day 16 postinfection, mice of either genotype were stably colonized with the pathogen, but fecal bacterial loads were approximately 0.5-2.0 log lower in TLR-4(-/-) IL-10(-/-) as compared to IL-10(-/-) mice. A. butzleri-infected TLR-4(-/-) IL-10(-/-) mice displayed less pronounced colonic apoptosis accompanied by lower numbers of macrophages and monocytes, T lymphocytes, regulatory T-cells, and B lymphocytes within the colonic mucosa and lamina propria as compared to IL-10(-/-) mice. Furthermore, colonic concentrations of nitric oxide, TNF, IL-6, MCP-1, and, remarkably, IFN-γ and IL-12p70 serum levels were lower in A. butzleri-infected TLR-4(-/-) IL-10(-/-) versus IL-10(-/-) mice. In conclusion, TLR-4 is involved in mediating murine A. butzleri infection. Further studies are needed to investigate the molecular mechanisms underlying Arcobacter-host interactions in more detail.
authors.affiliation: Institute of Food Hygiene, Freie Universität Berlin , Berlin, Germany.
authors.forename: Greta
authors.initials: G
authors.lastname: Gölz
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: Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Heimesaat
keywords: Arcobacter butzleri; Toll-like receptor-4; apoptosis; colon; gnotobiotic IL-10–/–; innate and adaptive immunity; lipooligosaccharide; lipopolysaccharide; mice; pro-inflammatory immune responses; systemic immune responses