{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T02:51:49Z","timestamp":1790304709005,"version":"4.1.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,11,1]],"date-time":"2019-11-01T00:00:00Z","timestamp":1572566400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>HSV-2 is a neurotropic virus that causes a persistent, lifelong infection that increases risk for other sexually transmitted infections. The vaginal epithelium is the first line of defense against HSV-2 and coordinates the immune response through the secretion of immune mediators, including the proinflammatory cytokine IL-36\u03b3. Previously, we showed that IL-36\u03b3 treatment promoted transient polymorphonuclear cell infiltration to the vaginal cavity and protected against lethal HSV-2 challenge. In this report, we reveal that IL-36\u03b3 specifically induces transient neutrophil infiltration but does not impact monocyte and macrophage recruitment. Using IL-36\u03b3\u2212\/\u2212 mice in a lethal HSV-2 challenge model, we show that neutrophil counts are significantly reduced at 1 and 2 d postinfection and that KC-mediated mature neutrophil recruitment is impaired in IL-36\u03b3\u2212\/\u2212 mice. Additionally, IL-36\u03b3\u2212\/\u2212 mice develop genital disease more rapidly, have significantly reduced survival time, and exhibit an increased incidence of hind limb paralysis that is linked to productive HSV-2 infection in the brain stem. IL-36\u03b3\u2212\/\u2212 mice also exhibit a significant delay in clearance of the virus from the vaginal epithelium and a more rapid spread of HSV-2 to the spinal cord, bladder, and colon. We further show that the decreased survival time and increased virus spread observed in IL-36\u03b3\u2212\/\u2212 mice are not neutrophil-dependent, suggesting that IL-36\u03b3 may function to limit HSV-2 spread in the nervous system. Ultimately, we demonstrate that IL-36\u03b3 is a key regulator of neutrophil recruitment in the vaginal microenvironment and may function to limit HSV-2 neuroinvasion.<\/jats:p>","DOI":"10.4049\/jimmunol.1900280","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T19:35:16Z","timestamp":1570044916000},"page":"2655-2664","source":"Crossref","is-referenced-by-count":16,"title":["IL-36\u03b3 Is a Key Regulator of Neutrophil Infiltration in the Vaginal Microenvironment and Limits Neuroinvasion in Genital HSV-2 Infection"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4942-0711","authenticated-orcid":false,"given":"Jameson K","family":"Gardner","sequence":"first","affiliation":[{"name":"Department of Basic Medical Sciences, University of Arizona College of Medicine\u2013Phoenix , Phoenix, AZ 85004"},{"name":"Molecular and Cellular Biology Graduate Program, School of Life Sciences, Arizona State University , Tempe, AZ 85287"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-0038","authenticated-orcid":false,"given":"Alison","family":"Swaims-Kohlmeier","sequence":"additional","affiliation":[{"name":"Laboratory Branch, Division of HIV\/AIDS Prevention, Centers for Disease Control and Prevention , Atlanta, GA 30333"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-5917","authenticated-orcid":false,"given":"Melissa M","family":"Herbst-Kralovetz","sequence":"additional","affiliation":[{"name":"Department of Basic Medical Sciences, University of Arizona College of Medicine\u2013Phoenix , Phoenix, AZ 85004"},{"name":"Department of Obstetrics and Gynecology, University of Arizona College of Medicine\u2013Phoenix , Phoenix, AZ 85004"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,11,15]]},"reference":[{"key":"2025030417544080800_r1","article-title":"Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. 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