Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA.
J Virol. 2013 Jun;87(12):7093-101. doi: 10.1128/JVI.00600-13. Epub 2013 Apr 17.
T helper 17 (Th17) cells play an important role in mucosal immune homeostasis and maintaining the integrity of the mucosal epithelial barrier. Loss of Th17 cells has been extensively documented during human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections. The lack of effective repopulation of Th17 cells has been associated with chronic immune activation mediated by the translocation of microbial products. Using ex vivo analysis of purified peripheral blood CD4 T cells from SIV-infected rhesus macaques, we show that the suppression of interleukin-17 (IL-17) expression correlated with upregulated expression of negative regulatory genes PIAS3, SHP2, and SOCS3 in CD4 T cells. Suppressed Th17 expression was accompanied by elevated levels of soluble CD14 (sCD14) and lipopolysaccharide binding protein (LBP) in the plasma during early stages of infection. Plasma viral loads rather than sCD14 or LBP levels correlated with acute immune activation. Additionally, we observed a significant increase in the expression of CD14 on peripheral blood monocytes that correlated with IL-23 expression and markers of microbial translocation. Taken together, our results provide new insights into the early events associated with acute SIV pathogenesis and suggest additional mechanisms playing a role in suppression of Th17 cells.
辅助性 T 细胞 17（Th17）在黏膜免疫稳态和维持黏膜上皮屏障完整性方面发挥着重要作用。在人类免疫缺陷病毒（HIV）和猴免疫缺陷病毒（SIV）感染期间，Th17 细胞的缺失已得到广泛证实。Th17 细胞缺乏有效的再增殖与微生物产物易位介导的慢性免疫激活有关。通过对 SIV 感染恒河猴外周血 CD4 T 细胞的体外分析，我们发现白细胞介素 17（IL-17）表达的抑制与 CD4 T 细胞中负调控基因 PIAS3、SHP2 和 SOCS3 的上调表达相关。在感染早期，Th17 表达受抑制的同时，血浆中可溶性 CD14（sCD14）和脂多糖结合蛋白（LBP）的水平升高。血浆病毒载量而不是 sCD14 或 LBP 水平与急性免疫激活相关。此外，我们观察到外周血单核细胞中 CD14 的表达显著增加，与 IL-23 表达和微生物易位标志物相关。总之，我们的研究结果为急性 SIV 发病机制相关的早期事件提供了新的见解，并提示了其他可能在抑制 Th17 细胞中发挥作用的机制。
