Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection.

Autor: Shang L; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Smith AJ; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Reilly CS; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA., Duan L; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Perkey KE; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Wietgrefe S; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Zupancic M; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Southern PJ; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA., Johnson RP; Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA., Carlis JV; Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA.; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, Minnesota, USA., Haase AT; Department of Microbiology and Immunology, Medical School, University of Minnesota, Minneapolis, Minnesota, USA.
Jazyk: angličtina
Zdroj: Mucosal immunology [Mucosal Immunol] 2018 Mar; Vol. 11 (2), pp. 512-522. Date of Electronic Publication: 2017 Aug 09.
DOI: 10.1038/mi.2017.69
Abstrakt: 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 24 h 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.
Databáze: MEDLINE
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