{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:45:52Z","timestamp":1778874352550,"version":"3.51.4"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T00:00:00Z","timestamp":1690848000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100012321","name":"AU | College of Veterinary Medicine, Auburn University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012321","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI153794"],"award-info":[{"award-number":["AI153794"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000053","name":"HHS | NIH | National Eye Institute","doi-asserted-by":"publisher","award":["EY035057"],"award-info":[{"award-number":["EY035057"]}],"id":[{"id":"10.13039\/100000053","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Herpetic stromal keratitis (HSK) is a painful and vision-impairing disease caused by recurrent HSV-1 infection of the cornea. The virus replication in the corneal epithelium and associated inflammation play a dominant role in HSK progression. Current HSK treatments targeting inflammation or virus replication are partially effective and promote HSV-1 latency, and long-term use can cause side effects. Thus, understanding molecular and cellular events that control HSV-1 replication and inflammation is crucial for developing novel HSK therapies. In this study, we report that ocular HSV-1 infection induces the expression of IL-27, a pleiotropic immunoregulatory cytokine. Our data indicate that HSV-1 infection stimulates IL-27 production by macrophages. Using a primary corneal HSV-1 infection mouse model and IL-27 receptor knockout mice, we show that IL-27 plays a critical role in controlling HSV-1 shedding from the cornea, the optimum induction of effector CD4+ T cell responses, and limiting HSK progression. Using in vitro bone marrow\u2013derived macrophages, we show that IL-27 plays an antiviral role by regulating macrophage-mediated HSV-1 killing, IFN-\u03b2 production, and IFN-stimulated gene expression after HSV-1 infection. Furthermore, we report that IL-27 is critical for macrophage survival, Ag uptake, and the expression of costimulatory molecules involved in the optimum induction of effector T cell responses. Our results indicate that IL-27 promotes endogenous antiviral and anti-inflammatory responses and represents a promising target for suppressing HSK progression.<\/jats:p>","DOI":"10.4049\/jimmunol.2200420","type":"journal-article","created":{"date-parts":[[2023,6,16]],"date-time":"2023-06-16T13:45:40Z","timestamp":1686923140000},"page":"474-485","source":"Crossref","is-referenced-by-count":6,"title":["Role of IL-27 in HSV-1\u2013Induced Herpetic Stromal Keratitis"],"prefix":"10.1093","volume":"211","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9269-3614","authenticated-orcid":false,"given":"Ferrin","family":"Antony","sequence":"first","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8864-8546","authenticated-orcid":false,"given":"Chetan","family":"Pundkar","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4289-3743","authenticated-orcid":false,"given":"Maninder","family":"Sandey","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amarjit","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5031-5818","authenticated-orcid":false,"given":"Amol","family":"Suryawanshi","sequence":"additional","affiliation":[{"name":"Department of Pathobiology, College of Veterinary Medicine, Auburn University , Auburn, AL"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2023,8,1]]},"reference":[{"key":"2025020406040308200_r1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.3390\/pathogens12030437","article-title":"Role of innate interferon responses at the ocular surface in herpes simplex virus-1-induced herpetic stromal keratitis","volume":"12","author":"Ren","year":"2023","journal-title":"Pathogens"},{"key":"2025020406040308200_r2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.preteyeres.2012.07.002","article-title":"Pathogenesis of herpes stromal keratitis \u2013 a focus on corneal neovascularization","volume":"33","author":"Gim\u00e9nez","year":"2013","journal-title":"Prog. 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Eye Res."},{"key":"2025020406040308200_r6","doi-asserted-by":"crossref","first-page":"766","DOI":"10.3389\/fimmu.2020.00766","article-title":"Pathogenesis of herpes stromal keratitis: immune inflammatory response mediated by inflammatory regulators","volume":"11","author":"Wang","year":"2020","journal-title":"Front. Immunol."},{"key":"2025020406040308200_r7","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2471\/BLT.19.237149","article-title":"Herpes simplex virus: global infection prevalence and incidence estimates, 2016","volume":"98","author":"James","year":"2020","journal-title":"Bull. World Health Organ."},{"key":"2025020406040308200_r8","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1001\/archopht.1989.01070020221029","article-title":"Epidemiology of ocular herpes simplex. Incidence in Rochester, Minn, 1950 through 1982","volume":"107","author":"Liesegang","year":"1989","journal-title":"Arch. 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