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We reasoned that increased serum S100A9 in SLE patients reflects accumulation of S100A9 protein in neutrophils and may indicate altered neutrophil function. In this study, we demonstrate elevated S100A9 protein within neutrophils from SLE patients, and MRL\/lpr mice associates with lower mitochondrial superoxide, decreased suicidal neutrophil extracellular trap formation, and increased susceptibility to Staphylococcus aureus infection. Furthermore, increasing mitochondrial superoxide production restored the antibacterial activity of MRL\/lpr neutrophils in response to S. aureus. These results demonstrate that accumulation of intracellular S100A9 associates with impaired mitochondrial homeostasis, thereby rendering SLE neutrophils inherently less bactericidal.<\/jats:p>","DOI":"10.4049\/jimmunol.2100752","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T11:00:22Z","timestamp":1639998022000},"page":"454-463","source":"Crossref","is-referenced-by-count":16,"title":["Altered Mitochondrial Homeostasis during Systemic Lupus Erythematosus Impairs Neutrophil Extracellular Trap Formation Rendering Neutrophils Ineffective at Combating\n                    <i>Staphylococcus aureus<\/i>"],"prefix":"10.1093","volume":"208","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7259-6574","authenticated-orcid":false,"given":"Andrew J","family":"Monteith","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3629-8323","authenticated-orcid":false,"given":"Jeanette M","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8973-2950","authenticated-orcid":false,"given":"Jonathan M","family":"Williams","sequence":"additional","affiliation":[{"name":"Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1732-2682","authenticated-orcid":false,"given":"Kelsey","family":"Voss","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4106-3396","authenticated-orcid":false,"given":"Jeffrey C","family":"Rathmell","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6347-5738","authenticated-orcid":false,"given":"Leslie J","family":"Crofford","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5094-8105","authenticated-orcid":false,"given":"Eric P","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Center for Immunobiology, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Division of Rheumatology and Immunology, Department of Medicine, Vanderbilt University Medical Center , Nashville, TN"},{"name":"Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center , Nashville, TN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,1,15]]},"reference":[{"key":"2025021008495631100_r1","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1086\/528716","article-title":"Are community-associated methicillin-resistant Staphylococcus aureus (MRSA) strains replacing traditional nosocomial MRSA strains?","volume":"46","author":"Popovich","year":"2008","journal-title":"Clin. 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