Group B Streptococcus CovR regulation modulates host immune signalling pathways to promote vaginal colonization.
Group B Streptococcus CovR regulation modulates host immune signalling pathways to promote vaginal colonization.
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DOI：
10.1111/cmi.12105
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发表时间：
2013-07
影响因子：
3.4
通讯作者：
Doran KS
中科院分区：
文献类型：
--
作者：
Patras KA;Wang NY;Fletcher EM;Cavaco CK;Jimenez A;Garg M;Fierer J;Sheen TR;Rajagopal L;Doran KS
无乳链球菌又称B组链球菌，是健康女性阴道常见的共生微生物。然而，在敏感宿主中，GBS可以转变为病原体，但促进这种转化的宿主和微生物因素尚不清楚。GBS COVR/S(CsrR/S)是一个双组分的调控系统，对包括黏附和毒素产生在内的关键毒力元件进行调控。我们对暴露于WT、COVR缺陷和毒素缺陷菌株的人阴道上皮细胞进行了整体转录谱分析，观察到COVR的调节不足以及随后毒素产生的增加导致宿主炎症反应的急剧增加，特别是在IL-8和CXCL2促进的细胞因子信号通路中。此外，我们观察到COVR的调节影响上皮细胞的附着和细胞内的侵袭。在我们的GBS阴道定植小鼠模型中，我们进一步证明了COVR调节促进了阴道持久性，因为感染COVR缺陷株导致宿主免疫反应增强，通过细胞因子的产生和中性粒细胞的激活来衡量。使用CXCR2 KO小鼠，我们确定这种免疫改变至少部分是通过CXCL2受体的信号发生的。综上所述，我们得出结论，COVR是GBS阴道定植的重要调节因子，这种调节功能的丧失可能导致感染过程中的炎性破坏。
Streptococcus agalactiae (Group B Streptococcus, GBS) is a frequent commensal organism of the vaginal tract of healthy women. However, GBS can transition to a pathogen in susceptible hosts, but host and microbial factors that contribute to this conversion are not well understood. GBS CovR/S (CsrR/S) is a two component regulatory system that regulates key virulence elements including adherence and toxin production. We performed global transcription profiling of human vaginal epithelial cells exposed to WT, CovR deficient, and toxin deficient strains, and observed that insufficient regulation by CovR and subsequent increased toxin production results in a drastic increase in host inflammatory responses, particularly in cytokine signaling pathways promoted by IL-8 and CXCL2. Additionally, we observed that CovR regulation impacts epithelial cell attachment and intracellular invasion. In our mouse model of GBS vaginal colonization, we further demonstrated that CovR regulation promotes vaginal persistence, as infection with a CovR deficient strain resulted in a heightened host immune response as measured by cytokine production and neutrophil activation. Using CXCr2 KO mice, we determined that this immune alteration occurs, at least in part, via signaling through the CXCL2 receptor. Taken together, we conclude that CovR is an important regulator of GBS vaginal colonization and loss of this regulatory function may contribute to the inflammatory havoc seen during the course of infection.
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影响因子：
3.4
作者：
Hickey, D. K.;Patel, M. V.;Fahey, J. V.;Wira, C. R.
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作者：
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通讯作者：
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