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The infection manifests itself as genital herpes but in rare cases it can cause meningitis. In this study, we used a murine model of HSV-2 meningitis to show that Fas and FasL are induced within the CNS upon HSV-2 infection, both on resident microglia and astrocytes and on infiltrating monocytes and lymphocytes. Mice lacking Fas or FasL had a more severe disease development with significantly higher morbidity, mortality, and an overall higher CNS viral load. In parallel, these Fas\/FasL-deficient mice showed a severely impaired infection-induced CNS inflammatory response with lower levels of infiltrating CD4+ T-cells, lower levels of Th1 cytokines and chemokines, and a shift in the balance between M1 and M2 microglia\/monocytes. In vitro, we confirmed that Fas and FasL is required for the induction of leucocyte apoptosis, but also show that the Fas\/FasL pathway is required for adequate cytokine and chemokine production by glial cells. In summary, our data show that the Fas\/FasL cell death receptor pathway is an important defense mechanism in the spinal cord as it down-regulates HSV-2-induced inflammation while at the same time promoting adequate anti-viral immune responses against infection.<\/jats:p>","DOI":"10.3390\/v16091363","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T03:51:06Z","timestamp":1724730666000},"page":"1363","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Fas\/FasL-Mediated Apoptosis and Inflammation Contribute to Recovery from HSV-2-Mediated Spinal Cord Infection"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8409-3974","authenticated-orcid":false,"given":"Malgorzata","family":"Krzyzowska","sequence":"first","affiliation":[{"name":"Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Patrycy","sequence":"additional","affiliation":[{"name":"Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Chodkowski","sequence":"additional","affiliation":[{"name":"Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martyna","family":"Janicka","sequence":"additional","affiliation":[{"name":"Military Institute of Hygiene and Epidemiology, 01-163 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrzej","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"PORT Polish Center for Technology Development, 54-066 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Skulska","sequence":"additional","affiliation":[{"name":"PORT Polish Center for Technology Development, 54-066 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1185-283X","authenticated-orcid":false,"given":"Karolina","family":"Th\u00f6rn","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Inflammation Research, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(91)90614-5","article-title":"The polypeptide encoded by the cDNA for human cellsurface antigen Fas can mediate apoptosis","volume":"66","author":"Itoh","year":"1991","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.immuni.2009.01.001","article-title":"The many roles of FAS receptor signaling in the immune system","volume":"30","author":"Strasser","year":"2009","journal-title":"Immunity"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Ranjan, K., and Pathak, C. 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