Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection.
Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection.
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DOI：
10.1038/mi.2017.69
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发表时间：
2018-03
影响因子：
8
通讯作者：
Haase AT
中科院分区：
文献类型：
--
作者：
Shang L;Smith AJ;Reilly CS;Duan L;Perkey KE;Wietgrefe S;Zupancic M;Southern PJ;Johnson RP;Carlis JV;Haase AT
在naïve和SIVmac239Δnef-vaccinated动物中，宫颈阴道上皮分别通过启动或抑制促进传播的粘膜免疫反应，在决定病毒在雌性生殖道（FRT）传播的结果方面起着关键作用。在这项研究中，我们检测了幼年恒河猴和SIVmac239Δnef-vaccinated恒河猴阴道暴露于SIV后24小时内宫颈上皮的早期反应。通过体外和体内实验系统，我们发现阴道暴露于SIV可在上皮中迅速诱导广谱的促炎反应，这与NF-kB和糖皮质激素受体（GR）信号通路的相互调节有关。相反，在SIVmac239Δnef-vaccinated动物中，维持高水平GR表达和抑制上皮中NF-kB表达与FRT粘膜的免疫静止状态和对阴道攻击的保护有关。我们发现免疫静止状态是由fcgr2b -免疫复合物相互作用诱导的，这种相互作用改变了NF-kB和GR信号通路的相互调节。我们的研究结果表明，在早期宫颈阴道上皮反应中靶向NF-kB和GR信号的平衡可以调节阴道感染后的粘膜炎症和靶向细胞可用性，从而为当前的预防策略提供了一种补充方法。
Cervicovaginal epithelium plays a critical role in determining the outcome of virus transmission in the female reproductive tract (FRT) by initiating or suppressing transmission-facilitating mucosal immune responses in naïve and SIVmac239Δnef-vaccinated animals, respectively. In this study, we examined the very early responses of cervical epithelium within 24h after vaginal exposure to SIV in naive and SIVmac239Δnef-vaccinated rhesus macaques. Using both ex vivo and in vivo experimental systems, we found that vaginal exposure to SIV rapidly induces a broad spectrum of pro-inflammatory responses in the epithelium associated with a reciprocal regulation of NF-kB and glucocorticoid receptor (GR) signaling pathways. Conversely, maintenance of high-level GR expression and suppression of NF-kB expression in the epithelium were associated with an immunologically quiescent state in the FRT mucosa and protection against vaginal challenge in SIVmac239Δnef-vaccinated animals. We show that the immunologically quiescent state is induced by FCGR2B-Immune complexes interactions that modify the reciprocal regulation of NF-kB and GR signaling pathways. Our results suggest that targeting the balance of NF-kB and GR signaling in early cervicovaginal epithelium responses could moderate mucosal inflammation and target cell availability after vaginal infection, thereby providing a complementary approach to current prevention strategies.
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DOI：
10.4049/jimmunol.1500156
发表时间：
2016-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Zeng M;Smith AJ;Shang L;Wietgrefe SW;Voss JE;Carlis JV;Li Q;Piatak M Jr;Lifson JD;Johnson RP;Haase AT
通讯作者：
Haase AT
粘膜对SIV的粘膜反应中的上皮免疫细胞轴。
影响因子：
8
作者：
Shang L;Duan L;Perkey KE;Wietgrefe S;Zupancic M;Smith AJ;Southern PJ;Johnson RP;Haase AT
通讯作者：
Haase AT
影响因子：
64.8
作者：
Li, Qingsheng;Estes, Jacob D.;Schlievert, Patrick M.;Duan, Lijie;Brosnahan, Amanda J.;Southern, Peter J.;Reilly, Cavan S.;Peterson, Marnie L.;Schultz-Darken, Nancy;Brunner, Kevin G.;Nephew, Karla R.;Pambuccian, Stefan;Lifson, Jeffrey D.;Carlis, John V.;Haase, Ashley T.
通讯作者：
Haase, Ashley T.
DOI：
10.4049/jimmunol.1400820
发表时间：
2014-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Li Q;Zeng M;Duan L;Voss JE;Smith AJ;Pambuccian S;Shang L;Wietgrefe S;Southern PJ;Reilly CS;Skinner PJ;Zupancic ML;Carlis JV;Piatak M Jr;Waterman D;Reeves RK;Masek-Hammerman K;Derdeyn CA;Alpert MD;Evans DT;Kohler H;Müller S;Robinson J;Lifson JD;Burton DR;Johnson RP;Haase AT
通讯作者：
Haase AT
DOI：
10.4049/jimmunol.1400822
发表时间：
2014-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Smith AJ;Wietgrefe SW;Shang L;Reilly CS;Southern PJ;Perkey KE;Duan L;Kohler H;Müller S;Robinson J;Carlis JV;Li Q;Johnson RP;Haase AT
通讯作者：
Haase AT