Campylobacter jejuni drives MyD88-independent interleukin-6 secretion via Toll-like receptor 2.
Gastrointestinal disease caused by Campylobacter jejuni is characterized by localized inflammation and the destruction of the epithelial cell barrier that forms host innate protection against pathogens. This can lead to an imbalance in fluid transport across the gastrointestinal tract, resulting in severe diarrhea. The mechanisms of host cell receptor recognition of C. jejuni and downstream immune signaling pathways leading to this inflammatory disease, however, remain unclear. The aim of this study was to analyze the mechanisms involved in C. jejuni induction of the acute-phase inflammatory response regulator interleukin-6 (IL-6). Polarized intestinal epithelial Caco-2 monolayers responded to infections with Salmonella enterica serovar Typhimurium and eight isolates of C. jejuni by an increase in levels of expression and secretion of IL-6. No such IL-6 response, however, was produced upon infection with the human commensal organism Lactobacillus rhamnosus GG. The IL-6 signaling pathway was further characterized using short interfering RNA complexes to block gene expression. The inhibition of myeloid differentiation primary response protein 88 (MyD88) expression in this manner did not affect C. jejuni-induced IL-6 secretion, suggesting a MyD88-independent route to IL-6 signal transduction in C. jejuni-infected human epithelial cells. However, a significant reduction in levels of IL-6 was evident in the absence of Toll-like receptor 2 (TLR-2) expression, implying a requirement for TLR-2 in C. jejuni recognition. Caco-2 cells were also treated with heat-inactivated and purified membrane components of C. jejuni to isolate the factor responsible for triggering IL-6 signaling. The results demonstrate that C. jejuni surface polysaccharides induce IL-6 secretion from intestinal epithelial cells via TLR-2 in a MyD88-independent manner.
Friis
Lorna M
LM
Department of Medical Microbiology and Immunology, University of Alberta, 1-63 Medical Sciences Building, Edmonton T6G 2H7, Alberta, Canada. lfriis@ualberta.ca
Keelan
Monika
M
Taylor
Diane E
DE
D000818:Animals; D018938:Caco-2 Cells; D016123:Campylobacter jejuni / Q000472:pathogenicity*; D002460:Cell Line; D004847:Epithelial Cells / Q000382:microbiology*; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000382:microbiology*; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*
D015850:Interleukin-6; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2