Signal transduction in Campylobacter jejuni-induced cytokine production

Abstract

SummaryCampylobacter jejuni is the leading cause of foodborne illness in the USA and one of the most common causes of diarrhoea worldwide. Central to its pathogenicity is its ability to induce the production of proinflammatory cytokines such as interleukin (IL)-8 in intestinal epithelial cells. Here, we demonstrated that C. jejuni infection of intestinal epithelial cells results in the activation of the ERK and p38 mitogen-activated protein kinases and that the ERK kinase pathway is essential for IL-8 production. We found that MAP kinase stimulation leading to IL-8 secretion requires C. jejuni gene products whose production is stimulated upon contact with epithelial cells. We also found that C. jejuni flagellin is a very poor stimulator of Toll-like receptor (TLR)-5 and therefore does not play a significant role in the stimulation of cytokine production.

Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells RequiresCampylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-κB

“…Another candidate is flagellin, a potential ligand for TLR5. However, previous studies showed that purified Campylobacter flagellin failed to induce IL-8 secretion in polarized T84 cells (9,58). Our finding that the flaA mutant, which is nonmotile and lacks flagellin A but not flagellin B expression, and the pflA mutant, which expresses flagellin but is not motile, caused similar (ϳ50%) reductions in IL-8 induction further argues against a role for secreted flagellin A in stimulating IL-8 secretion through TLR5.…”

“…For example, the flagellin of Salmonella serovar Typhimurium (17) and the LPS of S. flexneri (5) have been shown to be inducers of IL-8. However, the flagellin of C. jejuni has been reported to be ineffective in the induction of IL-8 secretion in human intestinal epithelial cells (27,58). Campylobacter-secreted cytolethal distending toxin (CDT) can induce IL-8 secretion (22).…”

“…Campylobacter-secreted cytolethal distending toxin (CDT) can induce IL-8 secretion (22). Additionally, C. jejuni-induced IL-8 secretion requires the viability of the bacteria (9, 21) and depends on C. jejuni gene products that are expressed upon contact with epithelial cells and on the activation of the mitogen-activated protein kinase extracellular signal-regulated kinase in epithelial cells (58).…”

The Human Milk Oligosaccharide 2′-Fucosyllactose Quenches Campylobacter jejuni–Induced Inflammation in Human Epithelial Cells HEp-2 and HT-29 and in Mouse Intestinal Mucosa

“…Elevated synthesis and release of IL-8 is a characteristic innate immune response of HECs to enteric infection (5,(41)(42)(43)(44). A virulent strain of S. typhimurium (American Type Culture Collection 14028 wild-type), but not the attenuated strain sipA 2 , induces Il8 mRNA synthesis and p38 MAPK within 6 h of infection in intestinal epithelial cells.…”

Involvement of Toll-like receptor 5 in the recognition of flagellated bacteria

“…The importance of TLR5 signaling in mucosal immunity has been highlighted by recent studies, where diverse human disorders have been attributed to the dysfunction of TLR5. It has been shown that a common stop codon polymorphism of TLR5 is associated with susceptibility to pneumonia caused by the flagellated bacterium Legionella pneumophila (16), whereas certain flagellated bacteria can escape from TLR5 recognition by amino acid change on flagellin and persist at the mucosal surfaces (17)(18)(19). Moreover, TLR5-dependent recognition of flagellin may play a role in the inappropriate mucosal immune response to commensal bacteria associated with inflammatory bowel disease, such as Crohn's disease (20,21).…”