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However, whether neutrophils can exert fungicidal activity against C. gattii remains to be elucidated. Therefore, in this study, we investigated the neutrophil-mediated fungicidal effect against C. gattii R265 in vitro and compared it to the related fungal pathogen, Cryptococcus neoformans standard strain H99. We found that neutrophils recognized, phagocytosed, and killed C. gattii R265 in the presence of fresh mouse serum. This antifungal effect required phagocytosis and serine protease activity but not nicotinamide adenine dinucleotide phosphate oxidase activity. We also demonstrated that C. gattii R265 was more resistant to oxidative and nitrosative stress than C. neoformans H99. Together, these findings indicate that neutrophils can exert fungicidal activity against highly virulent C. gattii, at least under in vitro conditions.<\/jats:p>","DOI":"10.1093\/mmy\/myy153","type":"journal-article","created":{"date-parts":[[2018,12,13]],"date-time":"2018-12-13T22:45:37Z","timestamp":1544741137000},"page":"1046-1054","source":"Crossref","is-referenced-by-count":15,"title":["Neutrophil-mediated antifungal activity against highly virulent Cryptococcus gattii strain R265"],"prefix":"10.1093","volume":"57","author":[{"given":"Keigo","family":"Ueno","sequence":"first","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162\u20138640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nao","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162\u20138640, Japan"},{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125\u20138585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshiko","family":"Otani","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162\u20138640, Japan"},{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125\u20138585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiminori","family":"Shimizu","sequence":"additional","affiliation":[{"name":"Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo 125\u20138585, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuki","family":"Kinjo","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162\u20138640, Japan"},{"name":"Department of Bacteriology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105\u20138461, Japan"},{"name":"Jikei Center for Biofilm Science and Technology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 105\u20138461, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoshitsugu","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Department of Chemotherapy and Mycoses, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162\u20138640, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2019,1,18]]},"reference":[{"key":"2019100313120413700_bib1","doi-asserted-by":"crossref","first-page":"251","DOI":"10.3201\/eid1602.090900","article-title":"Epidemiology of Cryptococcus gattii, British Columbia, Canada, 1999\u20132007","volume":"16","author":"Galanis","year":"2010","journal-title":"Emerging Infect Dis"},{"key":"2019100313120413700_bib2","doi-asserted-by":"crossref","first-page":"e88875","DOI":"10.1371\/journal.pone.0088875","article-title":"Treatment and outcomes among patients with Cryptococcus gattii infections in the United States Pacific Northwest. 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