{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:51:46Z","timestamp":1790308306829,"version":"4.1.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000065","name":"HHS | NIH | National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["R01 NS107369"],"award-info":[{"award-number":["R01 NS107369"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Craniotomies are performed to treat a variety of intracranial pathology. Surgical site infection remains a complication of craniotomy despite the use of prophylactic antibiotics and universal sterile precautions. Infections occur in 1\u20133% of procedures, with approximately half caused by Staphylococcus aureus that forms a biofilm on the bone flap and is recalcitrant to systemic antibiotic therapy. We used an S. aureus-dsRed construct to compare the phagocytic capacity of leukocytes and microglia in vitro and in vivo using a mouse model of craniotomy infection. In addition, single-cell RNA sequencing (scRNA-seq) was applied to determine whether a transcriptional signature could be identified for phagocytic versus nonphagocytic cells in vivo. S. aureus was phagocytosed to equivalent extents in microglia, macrophages, neutrophils, and granulocytic myeloid-derived suppressor cells in vitro; however, microglial uptake of S. aureus was limited in vivo, whereas the other leukocyte populations exhibited phagocytic activity. scRNA-seq comparing the transcriptional signatures of phagocytic (S. aureus-dsRed+) versus nonphagocytic (S. aureus-dsRed\u2212) leukocytes identified classical pathways enriched in phagocytic cells (i.e., reactive oxygen species [ROS]\/reactive nitrogen species, lysosome, iron uptake, and transport), whereas nonphagocytic populations had increased ribosomal, IFN, and hypoxia signatures. scRNA-seq also revealed a robust ROS profile, which led to the exploration of craniotomy infection in NADPH oxidase 2 knockout mice. S. aureus burden, leukocyte recruitment, and intracellular bacterial load were significantly increased in NADPH oxidase 2 KO compared with wild-type animals. Collectively, these results highlight the importance of ROS generation in phagocytes for S. aureus biofilm containment, but not clearance, during craniotomy infection.<\/jats:p>","DOI":"10.4049\/jimmunol.2200503","type":"journal-article","created":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T05:01:46Z","timestamp":1672722106000},"page":"1973-1986","source":"Crossref","is-referenced-by-count":23,"title":["Transcriptional Profiling of Phagocytic Leukocytes and Microglia Reveals a Critical Role for Reactive Oxygen Species in Biofilm Containment during <i>Staphylococcus aureus<\/i> Craniotomy Infection"],"prefix":"10.1093","volume":"209","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9966-5501","authenticated-orcid":false,"given":"Joseph","family":"Menousek","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8384-4839","authenticated-orcid":false,"given":"Christopher M","family":"Horn","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cortney E","family":"Heim","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6015-8411","authenticated-orcid":false,"given":"Zachary","family":"Van Roy","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lee E","family":"Korshoj","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7624-670X","authenticated-orcid":false,"given":"Tammy","family":"Kielian","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology, University of Nebraska Medical Center , Omaha, NE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,15]]},"reference":[{"key":"2025021008413791500_r1","article-title":"Craniotomy","author":"Fern\u00e1ndez-de Thomas"},{"key":"2025021008413791500_r2","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1086\/518580","article-title":"Postoperative central nervous system infection: incidence and associated factors in 2111 neurosurgical procedures","volume":"45","author":"McClelland","year":"2007","journal-title":"Clin. 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