The differential pathological outcome between Chlamydia infection and vaccination is mediated by microRNA dysregulation

Abstract

Abstract Previous studies found that in contrast to immunization with an IL-10 knockout dendritic cell (DC)-based cellular or Vibrio cholerae ghost (VCG)-based subunit vaccine, immunization with live chlamydial elementary bodies does not protect against upper genital tract pathology following Chlamydia genital infection. The molecular mechanism regulating live Chlamydia- and vaccine-induced immunity is currently incompletely understood. To elucidate the mechanisms underlying this intriguing outcome, we examined the characteristic miRNA expression profiles in the upper genital tract (UGT) tissues of mice after immunization with live, subunit and DC-based Chlamydia vaccines using the NanoString nCounter Mouse miRNA assay. There were notable differences in miRNA expression profiles after immunization with the different vaccine formulations, with the DC vaccine-immunized group showing the highest number of uniquely differentially expressed (DE) miRNAs. Only 2 miRNAs, miR-146a and miR-2140 were commonly expressed in the genital tracts of the 3 immunization groups. Pathway analysis showed that the DE miRNAs regulate a number of pathways involved in disease and biological functions and targeted genes regulating immune response and inflammation. A number of central focus molecules associated with the miRNAs, including E2F Transcription Factor 1 (E2F1), Peroxisome Proliferator Activated Receptor Alpha (PPARA), and Interferon gamma (IFNG) were identified. Taken together, the results suggest that miRNA dysregulation plays an important role in the pathological outcome associated with chlamydial infection versus vaccination.