Choriodecidual Group B Streptococcal infection induces miR-155-5p in the fetal lung in Macaca nemestrina.

Publication Type:

Journal Article


Infection and immunity (2015)


Mechanisms underlying fetal lung injury remain poorly defined. MicroRNAs (miRNAs) are small non-coding, endogenous RNAs that regulate gene expression and have been implicated in the pathogenesis of lung disease. Using a nonhuman primate model of choriodecidual infection, we sought to determine if differentially expressed miRNAs were associated with acute fetal lung injury. After inoculating ten chronically catheterized pregnant monkeys (Macaca nemestrina) with either Group B Streptococcus (GBS) 1 x 10(6) colony forming units (n=5) or saline (n=5) in the choriodecidual space, we extracted fetal lung mRNA and miRNA and profiled changes in expression by microarray. We identified 9 differentially expressed miRNAs in GBS-exposed fetal lungs, but of these only miR-155-5p was validated by qRT-PCR (p=0.02). Significantly elevated miR-155-5p expression was also observed when immortalized human fetal airway epithelial (FeAE) cells were exposed to pro-inflammatory cytokines (IL-6 and TNF-α). Overexpression of miR-155-5p in FeAE cells in turn increased the production of IL-6, CXCL10/IP-10, which are implicated in leukocyte recruitment, but also in protection from lung injury. Interestingly, while miR-155-5p decreased FGF9 expression in a luciferase reporter assay, FGF9 levels were actually increased in GBS exposed fetal lungs in vivo. FGF9 overexpression is associated with abnormal lung development. Thus, upregulation of miR-155-5p may serve as a compensatory mechanism to lessen the increase in FGF9 and prevent aberrant lung development. Understanding the complicated networks regulating lung development in the setting of infection is a key step in identifying how to prevent fetal lung injury leading to bronchopulmonary dysplasia.