Expression of TLR 2, TLR 4 and iNOS in cervical monocytes of Chlamydia trachomatis-infected women and their role in host immune response.

PROBLEM: To study the innate immune response -TLR2 TLR 4 and iNOS expression in female genital Chlamydia trachomatis infection.

METHOD: TLR 2, TLR 4, and iNOS expression was evaluated by real-time PCR in C. trachomatis-infected asymptomatic, mucopurulent cervicitis (MPC), and fertility disorders (FD) women. Expression of TLR signaling pathway genes was checked in vivo in C. trachomatis-infected cervical monocytes. Further, inos gene expression and nitric oxide release was assessed in vitro in THP-1 cell line upon chlamydial infection.

RESULTS

TLR2, TLR4, and iNOS expression was significantly (P < 0.05) higher in C. trachomatis-positive women with FD, MPC, and asymptomatic women, respectively, than in control. Chlamydial infection significantly upregulates CD86, TLR4, MyD88, IRAK2, nF-κB, IL-1,β and IL-12 genes. Expression of iNOS gene was found to be significantly (P < 0.05) high 12 hrs post-infection.

CONCLUSIONS

Chlamydia trachomatis stimulates innate immune cells by activation of TLR2/TLR 4. Overall data indicate that recognition by TLR4 helps in initiation of immune response while recognition by TLR2 leads to secretion of inflammatory cytokines while iNOS-induced nitric oxide production helps in clearing Chlamydia. These results are first to provide initial insights into how innate immune response operates in human cervical monocytes upon chlamydial infection.