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Persistent nasal carriage of <jats:italic>S.\u00a0aureus<\/jats:italic> is a risk factor for influenza virus\u2010induced secondary bacterial pneumonia. There is limited understanding of the factors that cause <jats:italic>S.\u00a0aureus<\/jats:italic> to shift from the upper to the lower respiratory tract and convert from a commensal organism to an invasive pathogen. Here we show that neutrophils actively prevent <jats:italic>S.\u00a0aureus<\/jats:italic> dissemination. Establishment of a mouse model of localized <jats:italic>S.\u00a0aureus<\/jats:italic> nasal carriage revealed variations in the longevity of persistence of <jats:italic>S.\u00a0aureus<\/jats:italic> isolates. Improved persistence within this site was associated with reduced nasal inflammation, less neutrophil egress into the airways and reduced neutrophil\u2013bacteria association. Neutrophil depletion of mice with localized <jats:italic>S.\u00a0aureus<\/jats:italic> nasal carriage triggered the development of an invasive <jats:italic>S.\u00a0aureus<\/jats:italic> infection. Moreover, utilizing a model of influenza\u2010induced staphylococcal pneumonia we showed that treatment with granulocyte\u2013colony\u2010stimulating factor, a potent enhancer of neutrophil number and function, significantly reduced bacterial loads in the lung and improved disease outcomes. These data reveal that neutrophils play an important and active role in confining <jats:italic>S.\u00a0aureus<\/jats:italic> to the upper respiratory tract and highlight the use of approaches that improve neutrophil function as effective strategies to attenuate morbidity associated with staphylococcal pneumonia.<\/jats:p>","DOI":"10.1111\/imcb.12343","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T18:14:35Z","timestamp":1587838475000},"page":"577-594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Neutrophils play an ongoing role in preventing bacterial pneumonia by blocking the dissemination of <i>Staphylococcus aureus<\/i> from the upper to the lower airways"],"prefix":"10.1111","volume":"98","author":[{"given":"Chenghao","family":"Ge","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"},{"name":"School of Medicine Tsinghua University Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian R","family":"Monk","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah C","family":"Monard","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James G","family":"Bedford","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Braverman","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy P","family":"Stinear","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M","family":"Wakim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology The University of Melbourne Peter Doherty Institute for Infection and Immunity Melbourne VIC 3000 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