Chlamydia trachomatis (CT) is the leading cause of human bacterial sexually transmitted infections and associated reproductive damage. Given the involvement of microRNAs (miRs) as immune regulators and that TLR2 and CD4+ T cells are associated with host defenses and clearance of CT, we analyzed the modulation of miRs in genital tracts (GT) following CT challenge of wild type (WT), TLR2 deficient (TLR2-/-) and CD4+ deficient (CD4-/-) C57BL/6 mice. CT elementary bodies (5X104 IFU) were inoculated intravaginally for analysis at days 6 (early infection) and 12 (established infection). GT were removed and divided into lower (LGT; vagina & cervix), and upper (UGT) regions for RNA extraction and immunopathology associated miR PCR analyses. Within the WT LGT at day 6, miRs significantly down-regulated were mir-125b-5p (-17.34 fold change), miR-16(-8.87), mir-214(-4.30), mir-182(-19.29), and miR-30c(-19.15) while miR-135a(+13.89) was significantly upregulated, profiles not exhibited by day 12 in LGT and UGT. Moreover, we found significant differences in regulation of miR-214(-3.45) and miR-125b-5p(+1.85) in TLR2-/- GT and miR-214(-2.20) and miR-135a(-2.46) in CD4-/- GT compared to WT mice. Of importance, in vitro knockdown analyses with specific inhibitors of these miRs resulted in 30-45% increase in CT infectivity. Overall, this first report provides for further investigation on contribution of host miRs in CT ascension, associated inflammation and reproductive pathology.
- Copyright © 2013 by The American Association of Immunologists, Inc.