Poly (I:C) and LPS induce distinct immune responses by ovarian stromal fibroblasts.

ABSTRACT

Despite its anatomical location, the ovary is a site of pathogen exposure in the human female reproductive tract (FRT). However, the role of ovarian stromal fibroblasts in immune protection is unclear. We generated a population of ovarian stromal fibroblasts derived from normal human ovaries that expressed the pattern recognition receptors TLR3, TLR4, RIG-I, & MDA5. Poly (IC) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials. Poly (IC) exclusively stimulated the expression of interferon (IFN) ß, IFNλ1, and the IFN-stimulated gene OAS2. Poly (IC) also significantly increased secretion of elafin, CCL20, and RANTES, but had no effect on SDF-1α. In contrast, LPS had no effect on IFN or ISG expression but significantly increased secretion of RANTES and SDF-1α. Secretions from poly (IC)-treated fibroblasts had both greater anti-HIV activity and induced higher levels of CD4 + T cell chemotaxis than those from LPS-treated cells. Our studies demonstrate a potential key role for ovarian fibroblasts in innate immune protection against incoming pathogens in the normal ovary.