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The success of<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>as a pathogen is highly related to its enormous capacity to evade the host immune response. The critical role of tumor necrosis factor alpha (TNF-\u03b1) in the initial host defense against systemic staphylococcal infection has been demonstrated in experimental models and may partially explain the lack of significant benefits observed in clinical trials attempting to neutralize this cytokine in septic patients.<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>protein A plays a key role in regulating inflammation through its ability to bind and signal through the TNF-\u03b1 receptor 1 (TNFR1). In this study, we demonstrate that<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>, via protein A-mediated signaling, induces early shedding of TNFR1, which precedes the secretion of TNF-\u03b1<jats:italic>in vitro<\/jats:italic>and<jats:italic>in vivo<\/jats:italic>. The results obtained using a protein A-deficient mutant and<jats:italic>tnfr1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>mice strongly suggest that the increased levels of soluble TNFR1 present during experimental<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>infection may neutralize circulating TNF-\u03b1 and impair the host inflammatory response. Early shedding of TNFR1 induced by protein A may constitute a novel mechanism by which<jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">S. aureus<\/jats:named-content>subverts the host immune response.<\/jats:p>","DOI":"10.1128\/iai.00593-13","type":"journal-article","created":{"date-parts":[[2013,9,4]],"date-time":"2013-09-04T01:46:59Z","timestamp":1378259219000},"page":"4200-4207","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":50,"title":["Shedding of Tumor Necrosis Factor Receptor 1 Induced by Protein A Decreases Tumor Necrosis Factor Alpha Availability and Inflammation during Systemic Staphylococcus aureus Infection"],"prefix":"10.1128","volume":"81","author":[{"given":"Constanza","family":"Giai","sequence":"first","affiliation":[{"name":"Instituto de Investigaciones en Microbiolog\u00eda y Parasitolog\u00eda M\u00e9dica (IMPaM), Consejo 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