PDF(Pubmed)
Abstract：
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.
摘要：
衣原体疫苗方法渴望诱导Th1细胞以获得最佳保护，尽管没有直接证据表明Th1介导的衣原体从女性生殖道（FRT）中清除。我们最近报道，T-bet缺陷小鼠可以正常解决原发性衣原体感染，破坏Th1细胞在衣原体免疫中的潜在保护作用。这里,我们表明，T-bet缺陷小鼠发展强大的Th17反应和小鼠Th17细胞缺陷表现出延迟的细菌清除，证明衣原体特异性Th17细胞代表了被低估的保护性群体。此外,Th2缺陷小鼠能有效清除宫颈阴道感染。此外，我们表明，非造血细胞对IFN-γ的感知对于衣原体免疫是必不可少的，然而，FRT中的细菌清除不需要CD4T细胞分泌IFN-γ。尽管Th1细胞不是衣原体清除所必需的，对衣原体的保护性免疫仍然依赖于MHCII类限制性CD4T细胞和IL-12p40。一起,这些数据表明IL-12p40依赖性CD4效应成熟对衣原体免疫至关重要，和Th17细胞在较小程度上，然而Th1和Th2细胞的发育都不重要。未来的衣原体疫苗接种工作将更有效，如果他们专注于诱导这种保护性CD4T细胞群体。
