Chlamydia trachomatis T3SS effector CT622 induces proinflammatory cytokines through TLR2/TLR4-mediated MAPKs/NF-κB pathways in THP-1 cells.

BACKGROUND:The pathogenesis of Chlamydia trachomatis (C. trachomatis) is associated with the induction of the host inflammatory response; however, the precise underlying molecular mechanisms remain poorly understood. METHODS:CT622, a T3SS effector protein, has an important role in the pathogenesis of C. trachomatis; however, little is understood as to whether CT622 can induce a host inflammatory response. Our findings demonstrate that CT622 induces the expression of interleukin-6 (IL-6) and interleukin-8 (IL-8). Mechanistically, these effects involved the activation of the mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB) signaling pathways. RESULTS:Interestingly, we also demonstrated that the suppression of toll-like receptor 4 (TLR4) using small interfering RNA (siRNA) markedly reduced the phosphorylation of ERK, p38, JNK, and IκBα, concomitant with a significant decrease in IL-6 and IL-8 secretion. Conversely, disruption of Toll-like receptor 2 (TLR2) abrogated the CT622-induced upregulation of IL-8 and ERK activation, whereas IL-6 expression and p38, JNK, and IκBα phosphorylation were unaffected. CONCLUSIONS:Taken together, these results indicate that CT622 contributes to the inflammatory response through the TLR2/TLR4-mediated MAPKs/NF-κB pathway, which provides insight into the molecular pathology of Chlamydia trachomatis infection.