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. 2019 Nov;12(6):1391-1403.
doi: 10.1038/s41385-019-0203-z. Epub 2019 Sep 24.

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 Joo #  1 , Aldina Suwanto #  1 , Ayuko Sato  1 , Rika Nakahashi-Ouchida  1   2 , Hiromi Mori  1   2 , Yohei Uchida  1   2 , Shintaro Sato  1   2   3 , Yosuke Kurashima  1   2   4   5   6 , Yoshikazu Yuki  1   2 , Kohtaro Fujihashi  1   2   7 , Yasushi Kawaguchi  8 , Hiroshi Kiyono  9   10   11   12
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Free article

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 Joo et al. Mucosal Immunol. 2019 Nov.
Free article

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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