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Eur J Microbiol Immunol (Bp). 2015 Nov 18;5(4):321-32. doi: 10.1556/1886.2015.00043. eCollection 2015 Dec.

Toll-Like Receptor-4 is Essential for Arcobacter Butzleri-Induced Colonic and Systemic Immune Responses in Gnotobiotic IL-10(-/-) Mice.

European journal of microbiology & immunology

Greta Gölz, Gül Karadas, André Fischer, Ulf B Göbel, Thomas Alter, Stefan Bereswill, Markus M Heimesaat

Affiliations

  1. Institute of Food Hygiene, Freie Universität Berlin , Berlin, Germany.
  2. Department of Microbiology and Hygiene, Charité - University Medicine Berlin , Berlin, Germany.

PMID: 26716021 PMCID: PMC4681360 DOI: 10.1556/1886.2015.00043

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.

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

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