{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:57:29Z","timestamp":1788235049456,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012306","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000}}],"reference-count":80,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["AI117535"],"award-info":[{"award-number":["AI117535"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["AI052474"],"award-info":[{"award-number":["AI052474"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005440","name":"Center for Scientific Review","doi-asserted-by":"publisher","award":["T32GM150375"],"award-info":[{"award-number":["T32GM150375"]}],"id":[{"id":"10.13039\/100005440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is a human-adapted pathogen that replicates by asymptomatically colonizing its host. <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> is also the causative agent of purulent skin and soft tissue infections as well as bloodstream infections that result in the metastatic seeding of abscess lesions in all organ tissues. Prolonged colonization, infection, disease relapse, and recurrence point to the versatile capacity of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> to bypass innate and adaptive immune defenses as well as the notion that some hosts fail to generate protective immune responses. Here, we find a genetic trait that provides protection against this pathogen. Mice lacking functional H2-O, the equivalent of human HLA-DO, inoculated with a mouse-adapted strain of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>, efficiently decolonize the pathogen. Further, these decolonized animals resist subsequent bloodstream challenge with methicillin-resistant <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>. A genetic approach demonstrates that T-cell dependent B cell responses are required to control <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> colonization and infection in H2-O-deficient mice. Reduced bacterial burdens in these animals correlate with increased titers and enhanced phagocytic activity of <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic>-specific antibodies. H2-O negatively regulates the loading of high affinity peptides on major histocompatibility class II (MHC-II) molecules. Thus, we hypothesize that immune responses against <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> are derepressed in mice lacking H2-O because more high affinity peptides are presented by MHC-II. We speculate that loss-of-function HLA-DO alleles may similarly control <jats:italic>S<\/jats:italic>. <jats:italic>aureus<\/jats:italic> replication in humans.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012306","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T18:00:45Z","timestamp":1717696845000},"page":"e1012306","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":5,"title":["Deficiency in non-classical major histocompatibility class II-like molecule, H2-O confers protection against Staphylococcus aureus in mice"],"prefix":"10.1371","volume":"20","author":[{"given":"Emily","family":"Cullum","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunys","family":"Perez-Betancourt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eirinaios","family":"Gkika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olaf","family":"Schneewind","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Missiakas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2924-6747","authenticated-orcid":true,"given":"Tatyana","family":"Golovkina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ppat.1012306.ref001","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections","volume":"339","author":"FD Lowy","year":"1998","journal-title":"New Engl J Med"},{"issue":"9","key":"ppat.1012306.ref002","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1038\/nrmicro3521","article-title":"Staphylococcal manipulation of host immune responses","volume":"13","author":"V Thammavongsa","year":"2015","journal-title":"Nature reviews Microbiology"},{"key":"ppat.1012306.ref003","article-title":"Staphylococcal protein A contributes to persistent colonization of mice with Staphylococcus aureus","author":"Y Sun","year":"2018","journal-title":"J Bacteriol"},{"issue":"6","key":"ppat.1012306.ref004","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1038\/s41579-023-00852-y","article-title":"Staphylococcus aureus host interactions and adaptation","volume":"21","author":"BP Howden","year":"2023","journal-title":"Nature reviews Microbiology"},{"issue":"7056","key":"ppat.1012306.ref005","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1016\/S0140-6736(58)92462-0","article-title":"Staphylococcal infection in a maternity hospital; epidemiology and control","volume":"2","author":"WA Gillespie","year":"1958","journal-title":"Lancet"},{"issue":"2","key":"ppat.1012306.ref006","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10096-008-0602-7","article-title":"Intestinal carriage of Staphylococcus aureus: how does its frequency compare with that of nasal carriage and what is its clinical impact?","volume":"28","author":"DS Acton","year":"2009","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"1","key":"ppat.1012306.ref007","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1128\/br.27.1.56-71.1963","article-title":"Healthy carriage of Staphylococcus aureus: its prevalence and importance.","volume":"27","author":"RE Williams","year":"1963","journal-title":"Bacteriol Rev."},{"issue":"3","key":"ppat.1012306.ref008","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1128\/CMR.10.3.505","article-title":"Nasal carriage of Staphylococcus aureus: epidemiology, underlying mechanisms, and associated risks","volume":"10","author":"J Kluytmans","year":"1997","journal-title":"Clin Microbiol Rev"},{"issue":"1","key":"ppat.1012306.ref009","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJM200101043440102","article-title":"Nasal carriage as a source of Staphylococcus aureus bacteremia. 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