Cryptococcus gattii Infection Dampens Th1 and Th17 Responses by Attenuating Dendritic Cell Function and Pulmonary Chemokine Expression in the Immunocompetent Hosts

<jats:title>ABSTRACT</jats:title><jats:p>Cryptococcal infections are primarily caused by two related fungal species:<jats:named-content content-type="genus-species">Cryptococcus neoformans</jats:named-content>and<jats:named-content content-type="genus-species">Cryptococcus gattii</jats:named-content>. It is well known that<jats:named-content content-type="genus-species">C. neoformans</jats:named-content>generally affects immunocompromised hosts; however,<jats:named-content content-type="genus-species">C. gattii</jats:named-content>infection can cause diseases in not only immunocompromised hosts but also immunocompetent individuals. While recent studies suggest that<jats:named-content content-type="genus-species">C. gattii</jats:named-content>infection could dampen pulmonary neutrophil recruitment and inflammatory cytokine production in immunocompetent hosts, the impact of<jats:named-content content-type="genus-species">C. gattii</jats:named-content>infection on the development of their adaptive T helper cell immune response has not been addressed. Here, we report that<jats:named-content content-type="genus-species">C. neoformans</jats:named-content>infection with highly virulent and less virulent strains preferentially induced pulmonary Th1 and Th17 immune responses in the host, respectively. However, fewer pulmonary Th1 and Th17 cells could be detected in mice infected with<jats:named-content content-type="genus-species">C. gattii</jats:named-content>strains. Notably, dendritic cells (DC) in mice infected with<jats:named-content content-type="genus-species">C. gattii</jats:named-content>expressed much lower levels of surface MHC-II and<jats:italic>Il12</jats:italic>or<jats:italic>Il23</jats:italic>transcripts and failed to induce effective Th1 and Th17 differentiation<jats:italic>in vitro</jats:italic>. Furthermore, the expression levels of<jats:italic>Ip10</jats:italic>and<jats:italic>Cxcl9</jats:italic>transcripts, encoding Th1-attracting chemokines, were significantly reduced in the lungs of mice infected with the highly virulent<jats:named-content content-type="genus-species">C. gattii</jats:named-content>strain. Thus, our data suggest that<jats:named-content content-type="genus-species">C. gattii</jats:named-content>infection dampens the DC-mediated effective Th1/Th17 immune responses and downregulates the pulmonary chemokine expression, thus resulting in the inability to mount protective immunity in immunocompetent hosts.</jats:p>