Toll-Like Receptor-4 Is Involved in Mediating Intestinal and Extra-Intestinal Inflammation in Campylobacter coli -Infected Secondary Abiotic IL-10 -/- Mice.

Human Campylobacter infections are emerging worldwide and constitute significant health burdens. We recently showed that the immunopathological sequelae in Campylobacter jejuni -infected mice were due to Toll-like receptor (TLR)-4 dependent immune responses induced by bacterial lipooligosaccharide (LOS). Information regarding the molecular mechanisms underlying Campylobacter coli -host interactions are scarce, however. Therefore, we analyzed C. coli -induced campylobacteriosis in secondary abiotic IL-10 ^-/- mice with and without TLR4. Mice were infected perorally with a human C. coli isolate or with a murine commensal Escherichia coli as apathogenic, non-invasive control. Independent from TLR4, C. coli and E. coli stably colonized the gastrointestinal tract, but only C. coli induced clinical signs of campylobacteriosis. TLR4 ^-/- IL-10 ^-/- mice, however, displayed less frequently fecal blood and less distinct histopathological and apoptotic sequelae in the colon versus IL-10 ^-/- counterparts on day 28 following C. coli infection. Furthermore, C. coli -induced colonic immune cell responses were less pronounced in TLR4 ^-/- IL-10 ^-/- as compared to IL-10 ^-/- mice and accompanied by lower pro-inflammatory mediator concentrations in the intestines and the liver of the former versus the latter. In conclusion, our study provides evidence that TLR4 is involved in mediating C. coli -LOS-induced immune responses in intestinal and extra-intestinal compartments during murine campylobacteriosis.