Morphological switch is tightly coupled with the pathogenesis of many dimorphic fungal pathogens. @entity1327 , the major causative agent of @entity1330 , mostly presents as the @entity375 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 @entity375 -to-hypha transition in @entity1327 . Activation of Znf2 promotes @entity364 in vivo. Here we demonstrated that the cryptococcal strain overexpressing ZNF2 elicited strong and yet temporally confined proinflammatory responses in the early stage of @entity281 . In contrast, exacerbated @entity32 in @entity19 infected with the wild-type (WT) strain showed that they were unable to control the @entity281 . Animals inoculated with this filamentous @entity1327 strain had fewer pulmonary eosinophils and CD11c(+) CD11b(+) cells than animals inoculated with WT @entity375 . Moreover, @entity19 infected with this strain developed protective @entity630 - 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 ZNF2-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 ZNF2 elicit protective host immune responses. These findings could facilitate future research on novel immunological therapies. IMPORTANCE: @entity1330 is one of the leading causes of @entity204 among @entity791 @entity1 . This disease presents a severe threat to public health. The current antifungal regimens are unsatisfactory in controlling or clearing the pathogen @entity1327 . Immunotherapies and/or vaccines could be a promising approach to prevent or manage this @entity66 . However, the lack of understanding of host-pathogen interactions during cryptococcal @entity281 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 @entity630 or Th17 responses. Importantly, we discovered that vaccination with either the viable or heat-killed form of ZNF2-overexpressing cells protected animals from the otherwise lethal @entity281 by the highly virulent clinical strain. Our study suggests that the fungal cellular component(s) of the ZNF2-overexpressing strain may provide potential vaccine candidate(s) for controlling the fatal disease.

Development of Protective Inflammation and Cell-Mediated Immunity against XXXX after Exposure to Hyphal Mutants.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity791 :: ('MESH:D000163', 'Disease') :: ['AIDS'] @entity66 :: ('MESH:D004194', 'Disease') :: ['deadly disease'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity1330 :: ('MESH:D016919', 'Disease') :: ['cryptococcal meningitis', 'Cryptococcal meningitis'] @entity1327 :: ('5207', 'Species') :: ['Cryptococcus', 'Cryptococcus neoformans'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infection'] @entity364 :: ('MESH:D009181', 'Disease') :: ['hyphal formation and abolishes fungal virulence'] @entity375 :: ('4932', 'Species') :: ['yeast'] @entity204 :: ('MESH:D003643', 'Disease') :: ['death'] @entity630 :: ('57314(Tax:10090)', 'Gene') :: ['Th1']
@entity1327 :: (5207,Species) :: ['Cryptococcus neoformans']
