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S. aureus produces an array of bicomponent pore-forming toxins that target and kill leukocytes, known collectively as the leukocidins. The contribution of these leukocidins to impair the development of anti\u2013S. aureus adaptive immunity and facilitate reinfection is unclear. Using a murine model of recurrent bacteremia, we demonstrate that infection with a leukocidin mutant results in increased levels of anti\u2013S. aureus antibodies compared with mice infected with the WT parental strain, indicating that leukocidins negatively impact the generation of anti\u2013S. aureus antibodies in vivo. We hypothesized that neutralizing leukocidin-mediated immune subversion by vaccination may shift this host-pathogen interaction in favor of the host. Leukocidin-immunized mice produce potent leukocidin-neutralizing antibodies and robust Th1 and Th17 responses, which collectively protect against bloodstream infections. Altogether, these results demonstrate that blocking leukocidin-mediated immune evasion can promote host protection against S. aureus bloodstream infection.<\/jats:p>","DOI":"10.1084\/jem.20190541","type":"journal-article","created":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T02:21:23Z","timestamp":1588990883000},"update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":32,"title":["Targeting leukocidin-mediated immune evasion protects mice from\n                    <i>Staphylococcus aureus<\/i>\n                    bacteremia"],"prefix":"10.1084","volume":"217","author":[{"given":"Kayan","family":"Tam","sequence":"first","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-0170","authenticated-orcid":true,"given":"Keenan A.","family":"Lacey","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph C.","family":"Devlin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryaline","family":"Coffre","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Sommerfield","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rita","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"O\u2019Malley","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4843-3791","authenticated-orcid":false,"given":"Sergei B.","family":"Koralov","sequence":"additional","affiliation":[{"name":"Department of Pathology, New York University Grossman School of Medicine, New York, NY 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6211-3292","authenticated-orcid":true,"given":"P\u2019ng","family":"Loke","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"},{"name":"Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7126-0489","authenticated-orcid":true,"given":"Victor J.","family":"Torres","sequence":"additional","affiliation":[{"name":"Department of Microbiology, New York University Grossman School of Medicine, New York, NY 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2020,6,30]]},"reference":[{"key":"2026041423505198400_bib66","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1093\/infdis\/jis462","article-title":"Lower Antibody Levels to Staphylococcus Aureus Exotoxins Are Associated With Sepsis in Hospitalized Adults With Invasive S. 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