These studies were prompted by several potential conflicting issues in human cryptococcal disease including 1) a presumed T-cell defect in previously healthy patients based on paradigms developed with HIV-associated infections, 2) the unknown contributions of microbiological control vs. dysfunctional/paradoxical immune responses in CNS disease and 3) the resultant ambiguities as to whether microbiological control should be intensified in severe cases with antifungals or augmentative cytokines such as IFN-γ or adjunctive immune suppression with steroids or other agents. This evidence concerns the gene IFNG and infection.