A role for the CCR5-CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization.
Mucosal Immunol
; 12(6): 1391-1403, 2019 11.
Article
de En
| MEDLINE
| ID: mdl-31551493
ABSTRACT
Our current study focused on elucidating the role of specific chemokine-receptor interactions in antigen (Ag)-specific immune cell migration from nasal to genital mucosal tissues. This cellular migration is critical to induce effective Ag-specific immune responses against sexually transmitted genital infections. In this study, nasal immunization with live attenuated HSV-2 TK- induced the upregulation of CCR5 expression in effector immune cells, including CD4+ T cells, in Ag-priming sites and vaginal tissue. The CCR5 ligands CCL3, CCL4, and CCL5 all showed upregulated expression in vaginal tissue; in particular, CCL5 expression was highly enhanced in the stromal cells of vaginal tissue after nasal immunization. Intravaginal blockade of CCL5 by using neutralizing antibody diminished the number of HSV-2-specific effector cells in the vagina. Furthermore, loss of CCR5, a receptor for CCL5, impaired the migration of nasally primed Ag-specific effector cells from the airway to vagina. Effector cells adoptively transferred from CCR5-deficient mice failed to migrate into vaginal tissue, consequently increasing recipient mice's susceptibility to HSV-2 vaginal infection. These results indicate that the CCR5-CCL5 chemokine pathway is required for the migration and retention of nasally primed Ag-specific effector cells in vagina for providing protective immunity against HSV-2 infection.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Vagin
/
Vaccins antiviraux
/
Lymphocytes T CD4/
/
Herpès génital
/
Herpèsvirus humain de type 2
/
Chimiokine CCL5
/
Immunité muqueuse
/
Récepteurs CCR5
/
Muqueuse
Limites:
Animals
Langue:
En
Journal:
Mucosal Immunol
Sujet du journal:
ALERGIA E IMUNOLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Japon