Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, NH, 03756, USA.
J Reprod Immunol. 2018 Jun;127:36-42. doi: 10.1016/j.jri.2018.05.001. Epub 2018 May 9.
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 (I:C) and LPS, respective mimics of viral and bacterial infections, selectively upregulated antiviral gene expression and secretion of chemokines and antimicrobials. Poly (I:C) exclusively stimulated the expression of interferon (IFN) β, IFNλ1, and the IFN-stimulated gene OAS2. Poly (I:C) 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 (I:C)-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.
尽管卵巢位于人体女性生殖道（FRT）中，但它是病原体暴露的部位。然而，卵巢基质成纤维细胞在免疫保护中的作用尚不清楚。我们从正常人类卵巢中生成了一群表达模式识别受体 TLR3、TLR4、RIG-I 和 MDA5 的卵巢基质成纤维细胞。多聚（I:C）和 LPS 分别模拟病毒和细菌感染，选择性地上调抗病毒基因表达和趋化因子和抗菌药物的分泌。多聚（I:C）仅刺激干扰素（IFN）β、IFNλ1 和 IFN 刺激基因 OAS2 的表达。多聚（I:C）还显著增加了 Elafin、CCL20 和 RANTES 的分泌，但对 SDF-1α 没有影响。相反，LPS 对 IFN 或 ISG 表达没有影响，但显著增加了 RANTES 和 SDF-1α 的分泌。与 LPS 处理的细胞相比，多聚（I:C）处理的成纤维细胞的分泌物具有更强的抗 HIV 活性，并诱导更高水平的 CD4+T 细胞趋化性。我们的研究表明，卵巢成纤维细胞在正常卵巢中对进入的病原体具有先天免疫保护的潜在关键作用。
