{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:24:05Z","timestamp":1791239045762,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2013,3,1]],"date-time":"2013-03-01T00:00:00Z","timestamp":1362096000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The fungus\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptococcus neoformans<\/jats:named-content>\n            has emerged as a major cause of meningoencephalitis worldwide. Host response to the fungus involves both innate and adaptive immunity, but fungal genes that modulate these processes are poorly understood. Previous studies demonstrated attenuated virulence of a mutant of a\n            <jats:underline>v<\/jats:underline>\n            irulence-\n            <jats:underline>a<\/jats:underline>\n            ssociated\n            <jats:underline>D<\/jats:underline>\n            EAD-box protein (\n            <jats:italic>VAD1<\/jats:italic>\n            ) in mice, despite normal growth at host temperatures, suggesting modulation of the immune response. In the present study, the\n            <jats:italic>\u0394vad1<\/jats:italic>\n            mutant demonstrated progressive clearance from lung and was unable to induce pathological lesions or to cause extrapulmonary disease, despite retaining its ability to grow in mouse serum and a J774.16 macrophage cell line. Pulmonary clearance occurred with a minimal cellular infiltrate, marked by reduced CD4 cells, CD11b\n            <jats:sup>+<\/jats:sup>\n            Ly6C\n            <jats:sup>high<\/jats:sup>\n            monocytes, and F4\/80\n            <jats:sup>+<\/jats:sup>\n            macrophages, but the mutant strain retained recruitment of CD8 cells, compared to infections with wild-type fungi. Adaptive cytokine responses were reduced, including Th1, Th2, and Th17 cytokines; however, early gamma interferon (IFN-\u03b3) and tumor necrosis factor alpha (TNF-\u03b1) responses were retained while nonprotective interleukin 4 (IL-4) and IL-5 were diminished. Furthermore, the\n            <jats:italic>\u0394vad1<\/jats:italic>\n            mutant was controlled in lungs despite CD4\/CD8 cell depletion. These data, along with improved phagocytosis by macrophages and increases in early\/innate IL-1\u03b1, IFN-\u03b3, and chemokines elicited in the lungs within 3 days of infection with the\n            <jats:italic>\u0394vad1<\/jats:italic>\n            mutant, indicate that\n            <jats:italic>VAD1<\/jats:italic>\n            expression reduces innate recognition of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. neoformans<\/jats:named-content>\n            , rendering the yeast resistant to elimination by the innate mechanisms of host defense. Thus, our studies define a novel role of the cryptococcal Vad1 protein as a central regulator of cryptococcal virulence and illustrate that Vad1 promotes microbe resistance to innate host defenses.\n          <\/jats:p>","DOI":"10.1128\/iai.00821-12","type":"journal-article","created":{"date-parts":[[2012,12,22]],"date-time":"2012-12-22T08:46:14Z","timestamp":1356165974000},"page":"777-788","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":16,"title":["Cryptococcus neoformans Growth and Protection from Innate Immunity Are Dependent on Expression of a Virulence-Associated DEAD-Box Protein, Vad1"],"prefix":"10.1128","volume":"81","author":[{"given":"Jin","family":"Qiu","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal A.","family":"Olszewski","sequence":"additional","affiliation":[{"name":"VA Medical Center, Ann Arbor, Ann Arbor, Michigan, USA"},{"name":"University of Michigan, Ann Arbor, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Williamson","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA"},{"name":"Section of Infectious Diseases, Immunology and International Medicine, University of Illinois College of Medicine, Chicago, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0b013e328322ffac"},{"key":"e_1_3_3_3_2","article-title":"Epidemiology of cryptococcal meningitis in the U.S.: 1997\u20132009","author":"Pyrgos V","unstructured":"PyrgosVSeitzAESteinerCAPrevotsDRWilliamsonPR. 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