Literature DB >> 31551493

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

Sunyi Joo1, Aldina Suwanto1, Ayuko Sato1, Rika Nakahashi-Ouchida1,2, Hiromi Mori1,2, Yohei Uchida1,2, Shintaro Sato1,2,3, Yosuke Kurashima1,2,4,5,6, Yoshikazu Yuki1,2, Kohtaro Fujihashi1,2,7, Yasushi Kawaguchi8, Hiroshi Kiyono9,10,11,12.   

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.

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Year:  2019        PMID: 31551493     DOI: 10.1038/s41385-019-0203-z

Source DB:  PubMed          Journal:  Mucosal Immunol        ISSN: 1933-0219            Impact factor:   7.313


  47 in total

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