{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T13:02:37Z","timestamp":1775912557318,"version":"3.50.1"},"reference-count":76,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T00:00:00Z","timestamp":1569888000000},"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":[[2019,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide to glutathione, which plays an important role in redox regulation. We have previously shown that Gsr facilitates neutrophil bactericidal activities and is pivotal for host defense against bacterial pathogens. However, it is unclear whether Gsr is required for immune defense against fungal pathogens. It is also unclear whether Gsr plays a role in immunological functions outside of neutrophils during immune defense. In this study, we report that Gsr\u2212\/\u2212 mice exhibited markedly increased susceptibility to Candida albicans challenge. Upon C. albicans infection, Gsr\u2212\/\u2212 mice exhibited dramatically increased fungal burden in the kidneys, cytokine and chemokine storm, striking neutrophil infiltration, histological abnormalities in both the kidneys and heart, and substantially elevated mortality. Large fungal foci surrounded by massive numbers of neutrophils were detected outside of the glomeruli in the kidneys of Gsr\u2212\/\u2212 mice but were not found in wild-type mice. Examination of the neutrophils and macrophages of Gsr\u2212\/\u2212 mice revealed several defects. Gsr\u2212\/\u2212 neutrophils exhibited compromised phagocytosis, attenuated respiratory burst, and impaired fungicidal activity in vitro. Moreover, upon C. albicans stimulation, Gsr\u2212\/\u2212 macrophages produced increased levels of inflammatory cytokines and exhibited elevated p38 and JNK activities, at least in part, because of lower MAPK phosphatase (Mkp)-1 activity and greater Syk activity. Thus, Gsr-mediated redox regulation is crucial for fungal clearance by neutrophils and the proper control of the inflammatory response by macrophages during host defense against fungal challenge.<\/jats:p>","DOI":"10.4049\/jimmunol.1701686","type":"journal-article","created":{"date-parts":[[2019,9,9]],"date-time":"2019-09-09T19:35:12Z","timestamp":1568057712000},"page":"2239-2251","source":"Crossref","is-referenced-by-count":22,"title":["Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation during Systemic <i>Candida albicans<\/i> Infection in Mice"],"prefix":"10.1093","volume":"203","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7320-554X","authenticated-orcid":false,"given":"Victoria Y","family":"Kim","sequence":"first","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abel","family":"Batty","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhui","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sean G","family":"Kirk","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara A","family":"Crowell","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Jin","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Microbial Infection and Immunity, The Ohio State University , Columbus, OH 43210"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9523-5296","authenticated-orcid":false,"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa , Iowa City, IA 52242"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3413-5379","authenticated-orcid":false,"given":"Lynette K","family":"Rogers","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Xiang","family":"Deng","sequence":"additional","affiliation":[{"name":"Ken and Ruth Davee Department of Neurology, Feinberg School of Medicine, Northwestern University , Chicago, IL 60611"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leif D","family":"Nelin","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43205"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yusen","family":"Liu","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, The Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital , Columbus, OH 43215"},{"name":"Department of Pediatrics, The Ohio State University College of Medicine , Columbus, OH 43205"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,10,15]]},"reference":[{"key":"2025030417543210700_r1","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1086\/591861","article-title":"NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007","volume":"29","author":"Hidron","year":"2008","journal-title":"Infect. 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