Journal
EUROPEAN JOURNAL OF MICROBIOLOGY AND IMMUNOLOGY
Volume 5, Issue 4, Pages 321-332Publisher
AKADEMIAI KIADO ZRT
DOI: 10.1556/1886.2015.00043
Keywords
Arcobacter butzleri; Toll-like receptor-4; lipopolysaccharide; lipooligosaccharide; gnotobiotic IL-10-/- mice; pro-inflammatory immune responses; systemic immune responses; colon; apoptosis; innate and adaptive immunity
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Funding
- German Research Foundation (DFG) [SFB633]
- German Federal Ministery of Education and Research (BMBF) [TP1.1]
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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-gamma 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.
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