Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice.
Th1 cells are dispensable for primary clearance of Chlamydia from the female reproductive tract of mice.
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Th1细胞可用于从小鼠的雌性生殖道的主要清除衣原体的主要清除。
DOI：
10.1371/journal.ppat.1010333
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发表时间：
2022-03
期刊：
影响因子：
6.7
通讯作者：
McSorley SJ
中科院分区：
文献类型：
--
作者：
Rixon JA;Depew CE;McSorley SJ
女性生殖道（FRT）对衣原体感染的保护性免疫反应尚不完全清楚。由于MHC ii类限制CD4 Th1反应能够分泌IFN-γ，因此被认为对细菌清除至关重要，但在衣原体感染的小鼠模型中尚未证明对表达t- β的Th1细胞的基本要求。在这里，我们研究了T-bet和IFN-γ在FRT感染后衣原体初步清除中的作用。令人惊讶的是，来自FRT的产生IFN-γ的CD4 T细胞在整个感染过程中表达低水平的T-bet，这表明经典的表达T-bet的Th1细胞产生效率低下，因此不太可能参与细菌清除。此外，T-bet表达不足或cd4特异性T-bet缺乏的小鼠清除了FRT感染，与野生型对照组相似。T-bet缺陷小鼠显示出明显的FRT CD4 T细胞向Th17反应倾斜，表明在缺乏Th1细胞的情况下会产生代偿效应途径。与此形成鲜明对比的是，IFN-γ-和IFN-γ- r缺陷小鼠能够减轻FRT细菌负荷，但会出现全身细菌传播和100%死亡率。总之，这些数据表明，IFN-γ信号对于保护小鼠免受致命性全身性疾病至关重要，但经典的表达t- bett的Th1细胞对于FRT内的初级清除不是必需的。探索Th1细胞对其他CD4效应谱系的保护作用可以为新衣原体疫苗的产生提供重要信息。CD4 Th1细胞产生IFN-γ被认为是清除女性生殖道衣原体（FRT）的关键，但这尚未得到正式测试。在这里，我们证明T-bet+ Th1细胞不是有效清除衣原体所必需的。此外，IFN-γ缺乏或消耗的影响主要是无法控制细菌的传播，而不是FRT的清除。总之，这些数据表明，与FRT控制相比，不同的免疫机制负责抑制细菌的全身传播。确定负责控制衣原体在FRT内复制的替代非th1 CD4效应机制可能是未来疫苗开发的基础。
Protective immune responses to Chlamydia infection within the female reproductive tract (FRT) are incompletely understood. MHC class II-restricted CD4 Th1 responses are believed to be vital for bacterial clearance due to their capacity to secrete IFN-γ, but an essential requirement for T-bet-expressing Th1 cells has yet to be demonstrated in the mouse model of Chlamydia infection. Here, we investigated the role of T-bet and IFN-γ in primary clearance of Chlamydia after FRT infection. Surprisingly, IFN-γ producing CD4 T cells from the FRT expressed low levels of T-bet throughout infection, suggesting that classical T-bet-expressing Th1 cells are inefficiently generated and therefore unlikely to participate in bacteria clearance. Furthermore, mice deficient in T-bet expression or with a CD4-specific T-bet deficiency cleared FRT infection similarly to wild-type controls. T-bet-deficient mice displayed significant skewing of FRT CD4 T cells towards Th17 responses, demonstrating that compensatory effector pathways are generated in the absence of Th1 cells. In marked contrast, IFN-γ-, and IFN-γR-deficient mice were able to reduce FRT bacterial burdens, but suffered systemic bacterial dissemination and 100% mortality. Together, these data demonstrate that IFN-γ signaling is essential to protect mice from fatal systemic disease, but that classical T-bet-expressing Th1 cells are non-essential for primary clearance within the FRT. Exploring the protective contribution of Th1 cells versus other CD4 effector lineages could provide important information for the generation of new Chlamydia vaccines. The production of IFN-γ by CD4 Th1 cells is thought to be critical for the clearance of Chlamydia from the female reproductive tract (FRT), but this has not been formally tested. Here we demonstrate that T-bet+ Th1 cells are not essential for effective Chlamydia clearance. Furthermore, the impact of IFN-γ deficiency or depletion is largely observed as a failure to control bacterial dissemination, rather than clearance from the FRT. Together, these data suggest that different immunological mechanisms are responsible for restraining systemic spread of bacteria versus FRT control. Defining alternative non-Th1 CD4 effector mechanisms that are responsible for controlling Chlamydia replication within the FRT could be foundational for future vaccine development.
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影响因子：
5.4
作者：
Malaviarachchi, Priyangi A.;Mercado, Miguel A. B.;Li, Lin-Xi
通讯作者：
Li, Lin-Xi
DOI：
10.4049/jimmunol.1102764
发表时间：
2012-02-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Johnson RM;Kerr MS;Slaven JE
通讯作者：
Slaven JE
影响因子：
32.4
作者：
McSorley, SJ;Asch, S;Jenkins, MK
通讯作者：
Jenkins, MK
DOI：
10.4049/jimmunol.1002596
发表时间：
2010-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jayarapu K;Kerr M;Ofner S;Johnson RM
通讯作者：
Johnson RM
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