{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:14:59Z","timestamp":1789776899266,"version":"4.0.1"},"reference-count":88,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,26]],"date-time":"2025-02-26T00:00:00Z","timestamp":1740528000000},"content-version":"vor","delay-in-days":1305,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI141490"],"award-info":[{"award-number":["AI141490"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006812","name":"Center for Integrated Healthcare, U.S. Department of Veterans Affairs","doi-asserted-by":"publisher","award":["I01 BX002711"],"award-info":[{"award-number":["I01 BX002711"]}],"id":[{"id":"10.13039\/100006812","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Neutrophils, polymorphonuclear leukocytes (PMN), play a critical role in the innate immune response to Staphylococcus aureus, a pathogen that continues to be associated with significant morbidity and mortality. Neutrophil extracellular trap (NET) formation is involved in ensnaring and killing of S. aureus, but this host\u2013pathogen interaction also leads to host tissue damage. Importantly, NET components including neutrophil proteases are under consideration as therapeutic targets in a variety of disease processes. Although S. aureus lipoproteins are recognized to activate cells via TLRs, specific mechanisms of interaction with neutrophils are poorly delineated. We hypothesized that a lipoprotein-containing cell membrane preparation from methicillin-resistant S. aureus (MRSA-CMP) would elicit PMN activation, including NET formation. We investigated MRSA-CMP\u2013elicited NET formation, regulated elastase release, and IL-8 production in human neutrophils. We studied PMN from healthy donors with or without a common single-nucleotide polymorphism in TLR1, previously demonstrated to impact TLR2\/1 signaling, and used cell membrane preparation from both wild-type methicillin-resistant S. aureus and a mutant lacking palmitoylated lipoproteins (lgt). MRSA-CMP elicited NET formation, elastase release, and IL-8 production in a lipoprotein-dependent manner. TLR2\/1 signaling was involved in NET formation and IL-8 production, but not elastase release, suggesting that MRSA-CMP\u2013elicited elastase release is not mediated by triacylated lipoproteins. MRSA-CMP also primed neutrophils for enhanced NET formation in response to a subsequent stimulus. MRSA-CMP\u2013elicited NET formation did not require Nox2-derived reactive oxygen species and was partially dependent on the activity of peptidyl arginine deiminase (PAD). In conclusion, lipoproteins from S. aureus mediate NET formation via TLR2\/1 with clear implications for patients with sepsis.<\/jats:p>","DOI":"10.4049\/jimmunol.2100283","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T19:35:11Z","timestamp":1626896111000},"page":"966-973","source":"Crossref","is-referenced-by-count":26,"title":["Lipoproteins from <i>Staphylococcus aureus<\/i> Drive Neutrophil Extracellular Trap Formation in a TLR2\/1- and PAD-Dependent Manner"],"prefix":"10.1093","volume":"207","author":[{"given":"Jessica S","family":"Hook","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parth A","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0544-7421","authenticated-orcid":false,"given":"Aidan","family":"O\u2019Malley","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihua","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3876-4001","authenticated-orcid":false,"given":"Jeffrey S","family":"Kavanaugh","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-0096","authenticated-orcid":false,"given":"Alexander R","family":"Horswill","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado School of Medicine , Aurora, CO"},{"name":"Department of Veterans Affairs, Eastern Colorado Healthcare System , Aurora, CO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica G","family":"Moreland","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Texas Southwestern Medical Center , Dallas, TX"},{"name":"Department of Microbiology, University of Texas Southwestern Medical Center , Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,1]]},"reference":[{"key":"2025030418555866400_r1","doi-asserted-by":"crossref","first-page":"1973","DOI":"10.3201\/eid2111.150452","article-title":"USA300 methicillin-resistant Staphylococcus aureus, United States, 2000-2013","volume":"21","author":"Carrel","year":"2015","journal-title":"Emerg. 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