{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T01:22:24Z","timestamp":1789262544983,"version":"build-2803163510"},"reference-count":82,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"813","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,8,27]]},"abstract":"<jats:p>\n            Despite the well-described association of skin lesions with\n            <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n            , the distinct ability of clinical isolates to influence the local and systemic inflammatory response in a patient-specific manner is insufficiently characterized. In this study, we analyzed clinical recessive dystrophic epidermolysis bullosa (RDEB), which is characterized by wounds chronically colonized with\n            <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n            , to explore the relationship between inflammatory immune response and strain diversity. Children with RDEB (moderate phenotype,\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a05; severe phenotype,\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a010) and controls (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a018) were enrolled in the study. Profiling of plasma proteins (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a0800), immune cells (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a030 subsets and cytokine-producing cells), and cytokines (\n            <jats:italic toggle=\"yes\">n<\/jats:italic>\n            \u00a0=\u00a038) identified a specific inflammatory signature in severe disease. Furthermore, patients with severe RDEB presented a high frequency of interleukin-17A+ (IL-17A+) cells among CD4+ and mucosal-associated invariant T (MAIT) lymphocytes. Positive\n            <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n            cultures from the skin of patients with RDEB allowed whole-genome sequencing of patient strains and assessment of primary keratinocyte immune response upon bacterial challenge.\n            <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n            secretome and conditioned medium from keratinocytes challenged with\n            <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n            strains from patients with severe but not from those with moderate RDEB promoted strong activation and a pro\u2013IL-17 response in both CD4+ and MAIT cells. Our findings show that\n            <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n            strains isolated from patients with severe RDEB induce an IL-17\u2013skewed immune response and pave the way for precision microbiology to explain and predict the highly variable virulence potential of bacterial clinical isolates.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adq7985","type":"journal-article","created":{"date-parts":[[2025,8,27]],"date-time":"2025-08-27T17:58:41Z","timestamp":1756317521000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Immune response and clinical severity are shaped by skin-adapted\n            <i>Staphylococcus aureus<\/i>\n            in chronically infected patients"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1902-6943","authenticated-orcid":true,"given":"Anne","family":"Jamet","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."},{"name":"Department of Clinical Microbiology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker-Enfants Malades, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiali","family":"Fu","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1461-0075","authenticated-orcid":true,"given":"C\u00e9line","family":"Dietrich","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Immunoregulation and Immunopathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalia","family":"Bellon","sequence":"additional","affiliation":[{"name":"Department of Dermatology, AP-HP, H\u00f4pital Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, R\u00e9seaux national et Europ\u00e9en Maladies rares de la peau FIMARAD et ERN-skin, 75015 Paris, France."},{"name":"Centre de r\u00e9f\u00e9rence MAGEC (Maladies rares de la peau d\u2019origine g\u00e9n\u00e9tique), IHU Necker Hospital, Imagine Institut, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Messaouda","family":"Attailia","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Immunoregulation and Immunopathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elif","family":"Uyar","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Montabord","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iharilalao","family":"Dubail","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2848-1109","authenticated-orcid":true,"given":"Khanyisile","family":"Kunene","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Immunoregulation and Immunopathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Ferroni","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), H\u00f4pital Necker-Enfants Malades, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Polivka","sequence":"additional","affiliation":[{"name":"Department of Dermatology, AP-HP, H\u00f4pital Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, R\u00e9seaux national et Europ\u00e9en Maladies rares de la peau FIMARAD et ERN-skin, 75015 Paris, France."},{"name":"Centre de r\u00e9f\u00e9rence MAGEC (Maladies rares de la peau d\u2019origine g\u00e9n\u00e9tique), IHU Necker Hospital, Imagine Institut, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Dupuis","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Euphrasie","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phanie","family":"Leclerc-Mercier","sequence":"additional","affiliation":[{"name":"Department of Pathology, AP-HP, H\u00f4pital Necker-Enfants Malades, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Four","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Immunoregulation and Immunopathology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1813-7520","authenticated-orcid":true,"given":"Ines","family":"Metatla","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, Necker Proteomics, SFR Necker, Inserm US24, 75015 Paris, 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France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1038-0495","authenticated-orcid":true,"given":"Nicolas","family":"Mirouze","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Versailles Saint-Quentin-en-Yvelines, Unit\u00e9 1173, Laboratoire Infection et Inflammation, 78180 Montigny-le-Bretonneux, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5243-4861","authenticated-orcid":true,"given":"Alain","family":"Charbit","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7655-9685","authenticated-orcid":true,"given":"Mathieu","family":"Coureuil","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Host-Pathogen Integrative Biology, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4615-3953","authenticated-orcid":true,"given":"Fabienne","family":"Charbit-Henrion","sequence":"additional","affiliation":[{"name":"Laboratory of Medical Genetics, AP-HP, H\u00f4pital Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6801-7106","authenticated-orcid":true,"given":"Smail","family":"Hadj-Rabia","sequence":"additional","affiliation":[{"name":"Department of Dermatology, AP-HP, H\u00f4pital Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, R\u00e9seaux national et Europ\u00e9en Maladies rares de la peau FIMARAD et ERN-skin, 75015 Paris, France."},{"name":"Centre de r\u00e9f\u00e9rence MAGEC (Maladies rares de la 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France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Bodemer","sequence":"additional","affiliation":[{"name":"Department of Dermatology, AP-HP, H\u00f4pital Necker-Enfants Malades, Universit\u00e9 Paris Cit\u00e9, R\u00e9seaux national et Europ\u00e9en Maladies rares de la peau FIMARAD et ERN-skin, 75015 Paris, France."},{"name":"Centre de r\u00e9f\u00e9rence MAGEC (Maladies rares de la peau d\u2019origine g\u00e9n\u00e9tique), IHU Necker Hospital, Imagine Institut, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-2269","authenticated-orcid":true,"given":"Maria","family":"Leite-de-Moraes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades (INEM), Team Immunoregulation and Immunopathology, 75015 Paris, 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G. A. M. Koedijk, J. W. Back, J. Neef, A. Dreisbach, J. M. van Dijl, I. A. Bakker-Woudenberg, G. Buist, Active immunization with an octa-valent Staphylococcus aureus antigen mixture in models of S. aureus bacteremia and skin infection in mice. 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