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Bacterial infection is associated with increased morbidity and more rapid mortality in IPF patient populations, and pathogens such as methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA) are commonly isolated from the lungs of hospitalized patients with IPF. Despite this, the effects of fibrotic lung injury on critical immune responses to infection remain unknown. In the present study, we show that, like humans with IPF, fibrotic mice infected with MRSA exhibit increased morbidity and mortality compared with uninfected fibrotic mice. We determine that fibrosis conferred a defect in MRSA clearance compared with nonfibrotic mice, resulting from blunted innate immune responses. We show that fibrosis inhibited neutrophil intracellular killing of MRSA through impaired neutrophil elastase release and oxidative radical production. Additionally, we demonstrate that lung macrophages from fibrotic mice have impaired phagocytosis of MRSA. Our study describes potentially novel impairments of antimicrobial responses upon pulmonary fibrosis development, and our findings suggest a possible mechanism for why patients with IPF are at greater risk of morbidity and mortality related to infection.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.152690","type":"journal-article","created":{"date-parts":[[2022,1,6]],"date-time":"2022-01-06T12:01:26Z","timestamp":1641470486000},"source":"Crossref","is-referenced-by-count":32,"title":["Fibrotic lung disease inhibits immune responses to staphylococcal pneumonia via impaired neutrophil and macrophage function"],"prefix":"10.1172","volume":"7","author":[{"given":"Helen I.","family":"Warheit-Niemi","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0177-7850","authenticated-orcid":true,"given":"Summer J.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1367-1685","authenticated-orcid":true,"given":"Shuvasree","family":"SenGupta","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1518-1452","authenticated-orcid":true,"given":"Carole A.","family":"Parent","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3096-409X","authenticated-orcid":true,"given":"Xiaofeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David N.","family":"O\u2019Dwyer","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3051-745X","authenticated-orcid":true,"given":"Bethany B.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology and"},{"name":"Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30866-8"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201006-0894CI"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70101-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1183\/09059180.00000812"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012513-104706"},{"issue":"6","key":"B6","doi-asserted-by":"crossref","DOI":"10.1002\/cti2.1065","article-title":"A pathologic two-way street: how innate immunity impacts lung fibrosis and fibrosis impacts lung immunity","volume":"8","author":"Warheit-Niemi","year":"2019","journal-title":"Clin Transl Immunology"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/s12890-018-0642-4"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0168164"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00159709"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1186\/s12931-014-0109-y"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.resinv.2017.09.006"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201403-0541OC"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201809-1650OC"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00628-2018"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2012-202403"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70069-4"},{"key":"B17","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/978-1-4939-7113-8_2","article-title":"The blemoycin model of pulmonary fibrosis","volume":"1627","author":"Liu","year":"2017","journal-title":"Methods Mol Biol"},{"issue":"3","key":"B18","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/S0022-3565(25)13257-6","article-title":", Lazo JS. 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