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In the current study, we showed that neutrophils from calprotectin-deficient S100A9\u2212\/\u2212 mice have an impaired ability to inhibit Aspergillus fumigatus hyphal growth in vitro and in infected corneas in a murine model of fungal keratitis; however, the ability to inhibit hyphal growth was restored in S100A9\u2212\/\u2212 mice by injecting recombinant calprotectin. Furthermore, using recombinant calprotectin with mutations in either the Zn and Mn binding sites or the Mn binding site alone, we show that both zinc and manganese binding are necessary for calprotectin\u2019s antihyphal activity. In contrast to hyphae, we found no role for neutrophil calprotectin in uptake or killing of intracellular A. fumigatus conidia either in vitro or in a murine model of pulmonary aspergillosis. We also found that an A. fumigatus \u2206zafA mutant, which demonstrates deficient zinc transport, exhibits impaired growth in infected corneas and following incubation with neutrophils or calprotectin in vitro as compared with wild-type. Collectively, these studies demonstrate a novel stage-specific susceptibility of A. fumigatus to zinc and manganese chelation by neutrophil-derived calprotectin.<\/jats:p>","DOI":"10.4049\/jimmunol.1502037","type":"journal-article","created":{"date-parts":[[2015,11,19]],"date-time":"2015-11-19T03:33:17Z","timestamp":1447903997000},"page":"336-344","source":"Crossref","is-referenced-by-count":138,"title":["Zinc and Manganese Chelation by Neutrophil S100A8\/A9 (Calprotectin) Limits Extracellular <i>Aspergillus fumigatus<\/i> Hyphal Growth and Corneal Infection"],"prefix":"10.1093","volume":"196","author":[{"given":"Heather L","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology, University of California, Irvine , Irvine, CA 92697"},{"name":"Department of Physiology and Biophysics, University of California, Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anupam","family":"Jhingran","sequence":"additional","affiliation":[{"name":"Infectious Disease Service, Department of Medicine, Memorial Sloan\u2013Kettering Cancer Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chairut","family":"Vareechon","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"de Jesus Carrion","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Case Western Reserve University , Cleveland, OH 44106"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric P","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine , Nashville, TN 37232"},{"name":"Veterans Affairs Tennessee Valley Healthcare System , Nashville, TN 37212"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J","family":"Chazin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Vanderbilt University School of Medicine , Nashville, TN 37232"},{"name":"Center for Structural Biology, Vanderbilt University School of Medicine , Nashville, TN 37232"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Antonio","family":"Calera","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Funcional y Gen\u00f3mica, Centro Mixto del Consejo Superior de Investigaciones Cient\u00edficas y Universidad de Salamanca , 37002 Salamanca ,","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias M","family":"Hohl","sequence":"additional","affiliation":[{"name":"Infectious Disease Service, Department of Medicine, Memorial Sloan\u2013Kettering Cancer Center , New York, NY 10065"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Pearlman","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Case Western Reserve University , Cleveland, OH 44106"},{"name":"Department of Ophthalmology, University of California, Irvine , Irvine, CA 92697"},{"name":"Department of Physiology and Biophysics, University of California, Irvine , Irvine, CA 92697"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,1,1]]},"reference":[{"key":"2025030702110271300_r1","doi-asserted-by":"crossref","first-page":"165rv13","DOI":"10.1126\/scitranslmed.3004404","article-title":"Hidden killers: human fungal infections","volume":"4","author":"Brown","year":"2012","journal-title":"Sci. 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