A role for the CCR5–CCL5 interaction in the preferential migration of HSV-2-specific effector cells to the vaginal mucosa upon nasal immunization

Academic Article

Abstract

  • © 2019, Society for Mucosal Immunology. 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.
  • Published In

  • Mucosal Immunology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Joo S; Suwanto A; Sato A; Nakahashi-Ouchida R; Mori H; Uchida Y; Sato S; Kurashima Y; Yuki Y; Fujihashi K
  • Start Page

  • 1391
  • End Page

  • 1403
  • Volume

  • 12
  • Issue

  • 6