Key Points
Intravaginal neomycin can pull CD8 T cells to the vaginal mucosa.
Neomycin-recruited CD8 T cells become tissue resident and protect mice from HSV-2.
Neomycin can replace recombinant chemokine CXCL10 in prime and pull vaccine.
Abstract
The presence of tissue-resident memory T cells at barrier tissues is critical for long-lasting protective immune responses. Previous work has shown that tissue-resident memory T cells can be established by “pulling” virus-specific effector T cells from circulation to the genital mucosa via topical vaginal application of chemokines in mice. Once established, these cells protect hosts against genital herpes infection. We recently showed that vaginal application of aminoglycoside antibiotics induces robust activation of the IFN signaling pathway, including upregulation of chemokine expression within the tissue in mice. In this study, we show that a single topical application of neomycin, an inexpensive and vaginally nontoxic antibiotic, is sufficient to pull CD8 T cells to the vaginal mucosa and provide protection against genital herpes infection in mice.
Footnotes
This work was in part supported by the Howard Hughes Medical Institute (to A.I.) and by funding from the National Institutes of Health to (A.I.) (R01AI054359, R01EB000487, and R01AI127429). S.G. and P.L. are recipients of James Hudson Brown–Alexander Brown Coxe postdoctoral fellowships at Yale University.
The online version of this article contains supplemental material.
Abbreviations used in this article:
- TRM
- tissue-resident memory T cell
- WT
- wild-type.
- Received April 24, 2019.
- Accepted February 1, 2020.
- Copyright © 2020 by The American Association of Immunologists, Inc.
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