Protection against Cryptococcosis by Using a Murine Gamma Interferon-Producing<i>Cryptococcus neoformans</i>Strain

<jats:title>ABSTRACT</jats:title><jats:p>We evaluated cell-mediated immune (CMI) responses in mice given a pulmonary infection with a<jats:italic>Cryptococcus neoformans</jats:italic>strain engineered to produce the Th1-type cytokine gamma interferon (IFN-γ). Mice given a pulmonary infection with an IFN-γ-producing<jats:italic>C. neoformans</jats:italic>strain were able to resolve the primary infection and demonstrated complete (100%) protection against a second pulmonary challenge with a pathogenic<jats:italic>C. neoformans</jats:italic>strain. Pulmonary cytokine analyses showed that Th1-type/proinflammatory cytokine and chemokine expression were significantly higher and Th2-type cytokine expression was significantly lower in mice infected with the IFN-γ-producing<jats:italic>C. neoformans</jats:italic>strain compared to wild-type-infected mice. This increased pulmonary Th1-type cytokine expression was also associated with significantly lower pulmonary fungal burden and significantly higher pulmonary leukocyte and T-lymphocyte recruitment in mice infected with the IFN-γ-producing<jats:italic>C. neoformans</jats:italic>strain compared to wild-type-infected mice. Our results demonstrate that pulmonary infection of mice with a<jats:italic>C. neoformans</jats:italic>strain expressing IFN-γ results in the stimulation of local Th1-type anti-cryptococcal CMI responses and the development of protective host immunity against future pulmonary cryptococcal infections. The use of fungi engineered to produce host cytokines is a novel method to study immune responses to infection and may be useful in developing vaccine strategies in humans.</jats:p>