TOLL-LIKE RECEPTOR-4 DEPENDENT INTESTINAL GENE EXPRESSION DURING ARCOBACTER BUTZLERI INFECTION OF GNOTOBIOTIC IL-10 DEFICIENT MICE

We have previously shown that Arcobacter butzleri infection induces Toll-like receptor (TLR)-4 dependent immune responses in perorally infected gnotobiotic IL-10(-/-) mice. Here, we analyzed TLR-4-dependent expression of genes encoding inflammatory mediators and matrix-degrading gelatinases MMP-2 and-9 in the small and large intestines of gnotobiotic TLR-4-deficient IL-10(-/-) mice that were perorally infected with A. butzleri strains CCUG 30485 or C1, of human and chicken origin, respectively. At day 6 following A. butzleri infection, colonic mucin-2 mRNA, as integral part of the intestinal mucus layer, was downregulated in the colon, but not ileum, of IL-10(-/-) but not TLR-4(-/-)I L-10(-/-) mice. CCUG 30485 strain-infected TLR-4-deficient IL-10(-/-) mice displayed less distinctly upregulated IFN-gamma, IL-17A, and IL-1 beta mRNA levels in ileum and colon, which was also true for colonic IL-22. These changes were accompanied by upregulated colonic MMP-2 and ileal MMP-9 mRNA exclusively in IL-10(-/-) mice. In conclusion, TLR-4 is essentially involved in A. butzleri mediated modulation of gene expression in the intestines of gnotobiotic IL-10(-/-) mice.