Early MicroRNA Expression Profile as a Prognostic Biomarker for the Development of Pelvic Inflammatory Disease in a Mouse Model of Chlamydial Genital Infection

• DOI: 10.1128/mbio.01241-14
• Publication Date: 2014-06-25T06:34:01Z
• Authors: Laxmi Yeruva; Garry S. A. Myers; Nicole Spencer; Heather Huot Creasy; Nancy E. Adams; Anthony T. Maurelli; Grant R. McChesney; Mario A. Cleves; Jacques Ravel; Anne Bowlin; Roger G. Rank
• Keywords: CXCL1; CXCL2; Salpingitis; Pelvic inflammatory disease; CXCL9

ABSTRACT It is not currently possible to predict the probability of whether a woman with chlamydial genital infection will develop pelvic inflammatory disease (PID). To determine if specific biomarkers may be associated distinct pathotypes, we utilized two Chlamydia muridarum variants ( C. Var001 [CmVar001] and CmVar004) that differ in their abilities elicit upper tract pathology mouse model. CmVar004 has lower growth rate vitro induces only 20% C57BL/6 oviducts versus 83.3% CmVar001-infected mice. chemokine cytokine production within 24 h outcome pathology, levels 15 chemokines cytokines were measured. induced significantly CXCL1, CXCL2, tumor necrosis factor alpha (TNF-α), CCL2 comparison CmVar001 similar rRNA rs16 ) for Chlamydiae . A combination microRNA (miRNA) sequencing quantitative real-time PCR (qRT-PCR) analysis 134 inflammation-related miRNAs was performed postinfection chemokine/cytokine responses would also reflected miRNA expression profiles. Interestingly, 12 (miR-135a-5p, miR298-5p, miR142-3p, miR223-3p, miR299a-3p, miR147-3p, miR105, miR325-3p, miR132-3p, miR142-5p, miR155-5p, miR-410-3p) overexpressed during compared infection, inversely correlating respective responses. our knowledge, this first report demonstrating early elicited host can differentiate between pathological chlamydiae predictive disease. IMPORTANCE apparent an infecting population consists multiple genetic differing capabilities eliciting response; thus, it identify given virulence pathotype. are known regulate genes turn signaling pathways involved pathogenesis. Importantly, stable reflect tissue response therefore have potential severity. Currently, respect infections, there no way infected patient more or less likely PID. However, data presented study indicate profile virulent variant course increased risk disease, allowing aggressive treatment before significant develops.