{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T22:25:40Z","timestamp":1793139940786,"version":"4.5.0"},"reference-count":30,"publisher":"Rockefeller University Press","issue":"9","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,8,30]]},"abstract":"<jats:p>Neutrophils trap and kill bacteria by forming highly decondensed chromatin structures, termed neutrophil extracellular traps (NETs). We previously reported that histone hypercitrullination catalyzed by peptidylarginine deiminase 4 (PAD4) correlates with chromatin decondensation during NET formation. However, the role of PAD4 in NET-mediated bacterial trapping and killing has not been tested. Here, we use PAD4 knockout mice to show that PAD4 is essential for NET-mediated antibacterial function. Unlike PAD4+\/+ neutrophils, PAD4\u2212\/\u2212 neutrophils cannot form NETs after stimulation with chemokines or incubation with bacteria, and are deficient in bacterial killing by NETs. In a mouse infectious disease model of necrotizing fasciitis, PAD4\u2212\/\u2212 mice are more susceptible to bacterial infection than PAD4+\/+ mice due to a lack of NET formation. Moreover, we found that citrullination decreased the bacterial killing activity of histones and nucleosomes, which suggests that PAD4 mainly plays a role in chromatin decondensation to form NETs instead of increasing histone-mediated bacterial killing. Our results define a role for histone hypercitrullination in innate immunity during bacterial infection.<\/jats:p>","DOI":"10.1084\/jem.20100239","type":"journal-article","created":{"date-parts":[[2010,8,23]],"date-time":"2010-08-23T22:45:25Z","timestamp":1282603525000},"page":"1853-1862","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1418,"title":["PAD4 is essential for antibacterial innate immunity mediated by neutrophil extracellular traps"],"prefix":"10.1084","volume":"207","author":[{"given":"Pingxin","family":"Li","sequence":"first","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Lindberg","sequence":"additional","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary J.","family":"Kennett","sequence":"additional","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Xiong","sequence":"additional","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanming","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Eukaryotic Gene Regulation, Department of Biochemistry and Molecular Biology 1 , and 2"},{"name":"Department of Veterinary and Biomedical Sciences, Pennsylvania State University, University Park, PA 16802 1 , and 2"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,8,23]]},"reference":[{"key":"2023072601460722700_bib1","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1182\/blood-2009-05-221606","article-title":"Restoration of NET formation by gene therapy in CGD controls aspergillosis","volume":"114","author":"Bianchi","year":"2009","journal-title":"Blood."},{"key":"2023072601460722700_bib2","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1038\/nrmicro1710","article-title":"Beneficial suicide: why neutrophils die to make NETs","volume":"5","author":"Brinkmann","year":"2007","journal-title":"Nat. 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