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This yeast may grow freely in body fluids, but it also flourishes within host cells. Despite extensive research on cryptococcal pathogenesis, host genes involved in the initial engulfment of fungi and subsequent stages of infection are woefully understudied. To address this issue, we combined short interfering RNA silencing and a high-throughput imaging assay to identify host regulators that specifically influence cryptococcal uptake. Of 868 phosphatase and kinase genes assayed, we discovered 79 whose silencing significantly affected cryptococcal engulfment. For 25 of these, the effects were fungus specific, as opposed to general alterations in phagocytosis. Four members of this group significantly and specifically altered cryptococcal uptake; one of them encoded CaMK4, a calcium\/calmodulin-dependent protein kinase. Pharmacological inhibition of CaMK4 recapitulated the observed defects in phagocytosis. Furthermore, mice deficient in CaMK4 showed increased survival compared to wild-type mice upon infection with\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            . This increase in survival correlated with decreased expression of pattern recognition receptors on host phagocytes known to recognize\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            . Altogether, we have identified a kinase that is involved in\n            <jats:named-content content-type=\"genus-species\">C. neoformans<\/jats:named-content>\n            internalization by host cells and in host resistance to this deadly infection.\n          <\/jats:p>","DOI":"10.1128\/iai.00195-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:23Z","timestamp":1506990623000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":7,"title":["RNA Interference Screening Reveals Host CaMK4 as a Regulator of Cryptococcal Uptake and Pathogenesis"],"prefix":"10.1128","volume":"85","author":[{"given":"Deepa","family":"Srikanta","sequence":"first","affiliation":[{"name":"Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Camaron 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