{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:20:58Z","timestamp":1792678858998,"version":"4.5.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2017,9,1]],"date-time":"2017-09-01T00:00:00Z","timestamp":1504224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2017,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The immune response to Staphylococcus aureus infection in skin involves the recruitment of polymorphonuclear neutrophils (PMNs) from the bone marrow via the circulation and local granulopoiesis from hematopoietic stem and progenitor cells (HSPCs) that also traffic to infected skin wounds. We focus on regulation of PMN number and function and the role of pore-forming \u03b1-toxin (AT), a virulence factor that causes host cell lysis and elicits inflammasome-mediated IL-1\u03b2 secretion in wounds. Infection with wild-type S. aureus enriched in AT reduced PMN recruitment and resulted in sustained bacterial burden and delayed wound healing. In contrast, PMN recruitment to wounds infected with an isogenic AT-deficient S. aureus strain was unimpeded, exhibiting efficient bacterial clearance and hastened wound resolution. HSPCs recruited to infected wounds were unaffected by AT production and were activated to expand PMN numbers in proportion to S. aureus abundance in a manner regulated by TLR2 and IL-1R signaling. Immunodeficient MyD88-knockout mice infected with S. aureus experienced lethal sepsis that was reversed by PMN expansion mediated by injection of wild-type HSPCs directly into wounds. We conclude that AT-induced IL-1\u03b2 promotes local granulopoiesis and effective resolution of S. aureus\u2013infected wounds, revealing a potential antibiotic-free strategy for tuning the innate immune response to treat methicillin-resistant S. aureus infection in immunodeficient patients.<\/jats:p>","DOI":"10.4049\/jimmunol.1700649","type":"journal-article","created":{"date-parts":[[2017,7,22]],"date-time":"2017-07-22T00:25:31Z","timestamp":1500683131000},"page":"1772-1782","source":"Crossref","is-referenced-by-count":17,"title":["\u03b1-Toxin Regulates Local Granulocyte Expansion from Hematopoietic Stem and Progenitor Cells in <i>Staphylococcus aureus<\/i>\u2013Infected Wounds"],"prefix":"10.1093","volume":"199","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3704-5902","authenticated-orcid":false,"given":"Patrick C","family":"Falahee","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0721-7523","authenticated-orcid":false,"given":"Leif S","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8445-3749","authenticated-orcid":false,"given":"Mack B","family":"Reynolds","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-9232","authenticated-orcid":false,"given":"Mauricio","family":"Pirir","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5801-3996","authenticated-orcid":false,"given":"Bridget E","family":"McLaughlin","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center Flow Cytometry Shared Resource, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carly A","family":"Dillen","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johns Hopkins University School of Medicine , Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ambrose L","family":"Cheung","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth , Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lloyd S","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Johns Hopkins University School of Medicine , Baltimore, MD 21231"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-6611","authenticated-orcid":false,"given":"Scott I","family":"Simon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of California , Davis, Davis, CA 95616"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2017,9,1]]},"reference":[{"key":"2025030614291272600_r1","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1111\/j.1524-475X.2009.00489.x","article-title":"Staphylococcal biofilms impair wound healing by delaying reepithelialization in a murine cutaneous wound model","volume":"17","author":"Schierle","year":"2009","journal-title":"Wound Repair Regen."},{"key":"2025030614291272600_r2","doi-asserted-by":"crossref","first-page":"S350","DOI":"10.1086\/533591","article-title":"Pathogenesis of methicillin-resistant Staphylococcus aureus infection","volume":"46","author":"Gordon","year":"2008","journal-title":"Clin. 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