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However, our understanding of NK cell development, maturation and activation in the setting of fungal infections is preliminary at best. Sporotrichosis is an emerging worldwide\u2010distributed subcutaneous mycosis endemic in many countries, affecting humans and other animals and caused by various related thermodimorphic <jats:italic>Sporothrix<\/jats:italic> species, whose prototypical member is <jats:italic>Sporothrix schenckii<\/jats:italic>. We show that following systemic infection of BALB\/c mice with <jats:italic>S. schenckii sensu stricto<\/jats:italic>, NK cells displayed a more mature phenotype as early as 5 days post\u2010infection as judged by CD11b\/CD27 expression. At 10 days post\u2010infection, NK cells had increased expression of CD62 ligand (CD62L) and killer cell lectin\u2010like receptor subfamily G member 1 (KLRG1), but not of CD25 or CD69. Depletion of NK cells with anti\u2010asialo GM1 drastically impaired fungal clearance, leading to a more than eightfold increase in splenic fungal load accompanied by heightened systemic inflammation, as shown by augmented production of the pro\u2010inflammatory cytokines tumour necrosis factor\u2010<jats:italic>\u03b1<\/jats:italic>, interferon\u2010<jats:italic>\u03b3<\/jats:italic> and interleukin\u20106, but not interleukin\u201017A, in the spleen and serum. Our study is, to the best of our knowledge, the first to demonstrate that a fungal infection can drive NK cell maturation <jats:italic>in vivo<\/jats:italic> and that such cells are pivotal for <jats:italic>in vivo<\/jats:italic> protection against <jats:italic>S. schenckii<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/imm.12986","type":"journal-article","created":{"date-parts":[[2018,7,21]],"date-time":"2018-07-21T06:58:18Z","timestamp":1532156298000},"page":"467-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Natural killer cells are pivotal for <i>in vivo<\/i> protection following systemic infection by <i>Sporothrix schenckii<\/i>"],"prefix":"10.1111","volume":"155","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2282-7562","authenticated-orcid":false,"given":"Lucas Souza","family":"Ferreira","sequence":"first","affiliation":[{"name":"Department of Clinical Analysis Faculty of Pharmaceutical Sciences of 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