Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells
Uropathogenic Escherichia coli block MyD88-dependent and activate MyD88-independent signaling pathways in rat testicular cells
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DOI：
10.4049/jimmunol.180.8.5537
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发表时间：
2008-04-15
影响因子：
4.4
通讯作者：
Meinhardt, Andreas
中科院分区：
文献类型：
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作者：
Bhushan, Sudhanshu;Tchatalbachev, Svetlin;Meinhardt, Andreas
泌尿道致病性大肠杆菌 (UPEC) 是泌尿生殖道感染最常见的病因，也是免疫性男性不育的重要原因。我们检查了睾丸细胞中的 TLR 1-11 表达谱以及对 UPEC 感染的功能反应。所有睾丸细胞类型都表达至少两种 TLR 的 mRNA，特别是，在 UPEC 暴露后，睾丸巨噬细胞 (TM)、支持细胞 (SC)、管周细胞 (PTC) 和腹膜巨噬细胞 (PM) 中诱导 TLR4 的合成。尽管 MyD88 依赖性途径被激活（如 TM、SC、PTC 和 PM 中丝裂原激活蛋白激酶的磷酸化以及 PTC 和 PM 中 I kappa B α 的降解和 NF-kappa B 核易位所例证的），但 UPEC 治疗不会导致任何研究细胞中促炎性细胞因子 IL-1 α、IL-6 和 TNF-α 的分泌。此外，与 UPEC 共孵育后，PM 中非致病性共生大肠杆菌或 LPS 刺激产生的这些细胞因子被完全消除。相反，在 SC、PTC、TM 和 PM 中，UPEC 暴露导致 MyD88 独立信号传导的激活，如 IFN 相关因子 3 的核转移以及 I 型 IFN α 和 β、IFN-γ 诱导蛋白 10、MCP-1 和 RANTES 表达升高所证明的。我们得出的结论是，在该体外模型中，UPEC 可以在不同水平上主动抑制 MyD88 依赖性信号传导，以防止睾丸细胞分泌促炎性细胞因子。因此，睾丸先天免疫防御转变为类似抗病毒的 MyD88 独立反应。
Uropathogenic Escherichia coli (UPEC) is the most common etiological cause of urogenital tract infections and represents a considerable cause of immunological male infertility. We examined TLR 1-11 expression profiles in testicular cells and the functional response to infection with UPEC. All testicular cell types expressed mRNAs for at least two TLRs and, in particular, synthesis of TLR4 was induced in testicular macrophages (TM), Sertoli cells (SC), peritubular cells (PTC), and peritoneal macrophages (PM) after UPEC exposure. Even though MyD88-dependent pathways were activated as exemplified by phosphorylation of mitogen-activated protein kinases in TM, SC, PTC, and PM and by the degradation of I kappa B alpha and the nuclear translocation of NF-kappa B in PTC and PM, treatment with UPEC did not result in secretion of the proinfiammatory cytokines IL-1 alpha, IL-6, and TNF-alpha in any of the investigated cells. Moreover, stimulated production of these cytokines by nonpathogenic commensal E. coli or LPS in PM was completely abolished after coincubation with UPEC. Instead, in SC, PTC, TM, and PM, UPEC exposure resulted in activation of MyD88-independent signaling as documented by nuclear transfer of IFN-related factor-3 and elevated expression of type I IFNs alpha and beta, IFN-gamma-inducible protein 10, MCP-1, and RANTES. We conclude that in this in vitro model UPEC can actively suppress MyD88-dependent signaling at different levels to prevent proinfiammatory cytokine secretion by testicular cells. Thus, testicular innate immune defense is shifted to an antiviral-like MyD88-independent response.