School of Basic Medicine, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of Immunology, Shenzhen University School of Medicine, Shenzhen, China.
Biol Reprod. 2021 Jul 2;105(1):113-127. doi: 10.1093/biolre/ioab076.
Three major pathogenic states of the prostate, including benign prostatic hyperplasia, prostate cancer, and prostatitis, are related to the local inflammation. However, the mechanisms underlying the initiation of prostate inflammation remain largely unknown. Given that the innate immune responses of the tissue-specific cells to microbial infection or autoantigens contribute to local inflammation, this study focused on pattern recognition receptor (PRR)-initiated innate immune responses in mouse prostatic epithelial cells (PECs). Primary mouse PECs abundantly expressed Toll-like receptor 3 (TLR3), TLR4, TLR5, melanoma differentiation-associated protein 5 (MDA5), and IFN-inducible protein 16 (p204 in mouse). These PRRs can be activated by their respective ligands: lipopolysaccharide (LPS) and flagellin of Gram-negative bacteria for TLR4 and TLR5, polyinosinic-polycytidylic acid (poly(I:C)) for TLR3 and MDA5, and herpes simplex virus DNA analog (HSV60) for p204. LPS and flagellin predominantly induced the expression of inflammatory cytokines, including tumor necrosis factor alpha (TNFA), interleukin 6 (IL6), chemokines monocyte chemoattractant protein-1 (MCP1), and C-X-C motif chemokine 10 (CXCL10). Poly(I:C) and HSV60 predominantly induced the expression of type 1 interferons (IFNA and IFNB) and antiviral proteins: Mx GTPase 1, 2',5'-oligoadenylate synthetase 1, and IFN-stimulated gene 15. The replication of mumps virus in PECs was inhibited by type 1 IFN signaling. These findings provide insights into the mechanisms underlying innate immune response in the prostate.
前列腺的三种主要致病状态，包括良性前列腺增生、前列腺癌和前列腺炎，都与局部炎症有关。然而，前列腺炎症的起始机制在很大程度上仍然未知。鉴于组织特异性细胞对微生物感染或自身抗原的固有免疫反应有助于局部炎症，本研究专注于小鼠前列腺上皮细胞（PECs）中模式识别受体（PRR）引发的固有免疫反应。原代小鼠 PECs 丰富表达 Toll 样受体 3（TLR3）、TLR4、TLR5、黑色素瘤分化相关蛋白 5（MDA5）和干扰素诱导蛋白 16（p204）。这些 PRR 可以被它们各自的配体激活：革兰氏阴性菌的脂多糖（LPS）和鞭毛蛋白激活 TLR4 和 TLR5，多聚肌苷酸-多聚胞苷酸（poly(I:C)) 激活 TLR3 和 MDA5，单纯疱疹病毒 DNA 类似物（HSV60）激活 p204。LPS 和鞭毛蛋白主要诱导炎症细胞因子的表达，包括肿瘤坏死因子-α（TNFA）、白细胞介素 6（IL6）、趋化因子单核细胞趋化蛋白-1（MCP1）和 C-X-C 基序趋化因子 10（CXCL10）。poly(I:C) 和 HSV60 主要诱导 I 型干扰素（IFNA 和 IFNB）和抗病毒蛋白的表达：Mx GTPase 1、2'，5'-寡聚腺苷酸合成酶 1 和干扰素刺激基因 15。腮腺炎病毒在 PECs 中的复制被 I 型 IFN 信号抑制。这些发现为前列腺固有免疫反应的机制提供了深入了解。
