{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T05:22:36Z","timestamp":1782969756025,"version":"3.54.5"},"reference-count":66,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2015,10,6]],"date-time":"2015-10-06T00:00:00Z","timestamp":1444089600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2015,10,30]],"date-time":"2015-10-30T00:00:00Z","timestamp":1446163200000},"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":["mBio"],"published-print":{"date-parts":[[2015,10,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Morphological switch is tightly coupled with the pathogenesis of many dimorphic fungal pathogens.\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            , the major causative agent of cryptococcal meningitis, mostly presents as the yeast form but is capable of switching to the hyphal form. The filamentous form has long been associated with attenuated virulence, yet the underlying mechanism remains elusive. We previously identified the master regulator Znf2 that controls the yeast-to-hypha transition in\n            <jats:italic>Cryptococcus<\/jats:italic>\n            . Activation of Znf2 promotes hyphal formation and abolishes fungal virulence\n            <jats:italic>in vivo<\/jats:italic>\n            . Here we demonstrated that the cryptococcal strain overexpressing\n            <jats:italic>ZNF2<\/jats:italic>\n            elicited strong and yet temporally confined proinflammatory responses in the early stage of infection. In contrast, exacerbated inflammation in mice infected with the wild-type (WT) strain showed that they were unable to control the infection. Animals inoculated with this filamentous\n            <jats:italic>Cryptococcus<\/jats:italic>\n            strain had fewer pulmonary eosinophils and CD11c\n            <jats:sup>+<\/jats:sup>\n            CD11b\n            <jats:sup>+<\/jats:sup>\n            cells than animals inoculated with WT yeast. Moreover, mice infected with this strain developed protective Th1- or Th17-type T cell responses. These findings suggest that the virulence attenuation of the filamentous form is likely due to its elicitation of protective host responses. The antivirulence effect of Znf2 was independent of two previously identified factors downstream of Znf2. Interestingly, mucosal immunizations with high doses of\n            <jats:italic>ZNF2<\/jats:italic>\n            -overexpressing cells, either in the live or heat-killed form, offered 100% protection to the host from a subsequent challenge with the otherwise lethal clinical strain H99. Our results demonstrate that heat-resistant cellular components presented in cryptococcal cells with activated\n            <jats:italic>ZNF2<\/jats:italic>\n            elicit protective host immune responses. These findings could facilitate future research on novel immunological therapies.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Cryptococcal meningitis is one of the leading causes of death among AIDS patients. This disease presents a severe threat to public health. The current antifungal regimens are unsatisfactory in controlling or clearing the pathogen\n            <jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>\n            . Immunotherapies and\/or vaccines could be a promising approach to prevent or manage this deadly disease. However, the lack of understanding of host-pathogen interactions during cryptococcal infection greatly hampers the development of effective immunotherapies. In this study, we discovered that inoculation of cryptococcal cells with activated Znf2, a morphogenesis regulator and an antivirulence factor, could shift the host pathological Th2 responses to the protective Th1 or Th17 responses. Importantly, we discovered that vaccination with either the viable or heat-killed form of\n            <jats:italic>ZNF2<\/jats:italic>\n            -overexpressing cells protected animals from the otherwise lethal infection by the highly virulent clinical strain. Our study suggests that the fungal cellular component(s) of the\n            <jats:italic>ZNF2<\/jats:italic>\n            -overexpressing strain may provide potential vaccine candidate(s) for controlling the fatal disease.\n          <\/jats:p>","DOI":"10.1128\/mbio.01433-15","type":"journal-article","created":{"date-parts":[[2015,10,7]],"date-time":"2015-10-07T01:11:02Z","timestamp":1444180262000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Development of Protective Inflammation and Cell-Mediated Immunity against Cryptococcus neoformans after Exposure to Hyphal Mutants"],"prefix":"10.1128","volume":"6","author":[{"given":"Bing","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Biology, Texas A&amp;M University, College Station, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen 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