Vaccine-modified NF-kB and GR signaling in cervicovaginal epithelium correlates with protection.
Mucosal Immunol
; 11(2): 512-522, 2018 03.
Article
em En
| MEDLINE
| ID: mdl-28792003
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.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Vagina
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Vacinas Virais
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Receptores de Glucocorticoides
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Infecções por HIV
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Colo do Útero
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NF-kappa B
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Síndrome de Imunodeficiência Adquirida dos Símios
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HIV-1
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Vírus da Imunodeficiência Símia
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Vacinas contra a AIDS
Limite:
Animals
Idioma:
En
Revista:
Mucosal Immunol
Ano de publicação:
2018
Tipo de documento:
Article