Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells.
Elimination of Chlamydia muridarum from the female reproductive tract is IL-12p40 dependent, but independent of Th1 and Th2 cells.
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DOI：
10.1371/journal.ppat.1011914
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发表时间：
2024-01
期刊：
影响因子：
6.7
通讯作者：
中科院分区：
文献类型：
--
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尽管没有直接证据表明Th1介导的衣原体从女性生殖道（FRT）清除，但衣原体疫苗方法渴望诱导Th1细胞以获得最佳保护。我们最近报道了t- bet缺陷小鼠可以正常解决原发性衣原体感染，破坏了Th1细胞在衣原体免疫中的潜在保护作用。在这里，我们发现t- bet缺陷小鼠产生了强大的Th17反应，而Th17细胞缺陷小鼠表现出延迟的细菌清除，表明衣原体特异性Th17细胞代表了一个被低估的保护性群体。此外，th2缺陷小鼠能够清除宫颈阴道感染。此外，我们发现非造血细胞对IFN-γ的感知对于衣原体免疫至关重要，但细菌在FRT中的清除并不需要CD4 T细胞分泌IFN-γ。尽管Th1细胞不是衣原体清除所必需的，但对衣原体的保护性免疫仍然依赖于MHC ii类限制性CD4 T细胞和IL-12p40。总之，这些数据表明il -12p40依赖性CD4效应成熟对于衣原体免疫至关重要，Th17细胞在较小程度上至关重要，但Th1和Th2细胞的发育都不是关键。如果未来的衣原体疫苗接种工作侧重于诱导这种保护性CD4 T细胞群，将会更加有效。CD4 T细胞介导女性生殖道衣原体感染清除的机制尚不清楚。与流行的观点相反，我们实验室之前的工作表明，以T-bet表达为特征的Th1子集不是清除所必需的。在这里，我们探索了其他辅助性T细胞亚群，并确定Th2细胞同样不需要，而Th17细胞有助于早期感染清除。最终，细胞因子亚单位IL-12p40在驱动有效的CD4 T细胞应答中起着重要作用，而CD4 T细胞应答并不是由典型CD4亚群Th1、Th2或Th17身份精确定义的。因此，疫苗开发应侧重于这种il -12p40驱动的CD4 T细胞反应，而不是依赖于经典T辅助亚群的标记。
Chlamydia vaccine approaches aspire to induce Th1 cells for optimal protection, despite the fact that there is no direct evidence demonstrating Th1-mediated Chlamydia clearance from the female reproductive tract (FRT). We recently reported that T-bet-deficient mice can resolve primary Chlamydia infection normally, undermining the potentially protective role of Th1 cells in Chlamydia immunity. Here, we show that T-bet-deficient mice develop robust Th17 responses and that mice deficient in Th17 cells exhibit delayed bacterial clearance, demonstrating that Chlamydia-specific Th17 cells represent an underappreciated protective population. Additionally, Th2-deficient mice competently clear cervicovaginal infection. Furthermore, we show that sensing of IFN-γ by non-hematopoietic cells is essential for Chlamydia immunity, yet bacterial clearance in the FRT does not require IFN-γ secretion by CD4 T cells. Despite the fact that Th1 cells are not necessary for Chlamydia clearance, protective immunity to Chlamydia is still dependent on MHC class-II-restricted CD4 T cells and IL-12p40. Together, these data point to IL-12p40-dependent CD4 effector maturation as essential for Chlamydia immunity, and Th17 cells to a lesser extent, yet neither Th1 nor Th2 cell development is critical. Future Chlamydia vaccination efforts will be more effective if they focus on induction of this protective CD4 T cell population. The mechanism that CD4 T cells use to mediate clearance of Chlamydia infection in the female reproductive tract remains unclear. Contrary to prevailing ideas, previous work from our lab demonstrated that the Th1 subset characterized by T-bet expression is not required for clearance. Here, we explore other T helper subsets and determine that Th2 cells are likewise not required while Th17 cells contribute to the early phase of infection clearance. Ultimately, the cytokine subunit IL-12p40 plays a substantial role in driving an effective CD4 T cell response that is not neatly defined by canonical CD4 subset Th1, Th2, or Th17 identity. Vaccine development thus should focus on this IL-12p40-driven CD4 T cell response rather than relying on markers of classical T helper subsets.
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影响因子：
3.8
作者：
Jordan SJ;Bakshi RK;Brown LT;Chi X;Geisler WM
通讯作者：
Geisler WM
影响因子：
30.5
作者：
He Z;Ma J;Wang R;Zhang J;Huang Z;Wang F;Sen S;Rothenberg EV;Sun Z
通讯作者：
Sun Z
影响因子：
6.7
作者：
Asquith KL;Horvat JC;Kaiko GE;Carey AJ;Beagley KW;Hansbro PM;Foster PS
通讯作者：
Foster PS
DOI：
10.4049/jimmunol.1103032
发表时间：
2012-09-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Gondek DC;Olive AJ;Stary G;Starnbach MN
通讯作者：
Starnbach MN
影响因子：
32.4
作者：
Kaplan, MH;Schindler, U;Grusby, MJ
通讯作者：
Grusby, MJ