Interferon-gamma is required for innate immunity to Cryptosporidium parvumin mice

Although CD4 T cells are required for recovery from cryptosporidial infecti on, mice with severe combined immunodeficiency (SCID) remain infected for l ong periods without ill effect. In contrast, mice whose ability to use inte rferon(IFN)-gamma is impaired, by neutralization or gene knockout, experien ce heavy cryptosporidial infection that may lead to death. To determine whe ther the innate immunity of SCID mice to Cryptosporidium parvum (CP) requir es IFN-gamma, doubly immunodeficient C57BL/6 SCID-IFN-gamma knockout mice w ere bred. These mice experienced heavy CP infections of the gut; a signific antly greater number became moribund or died, compared with mice carrying t he SCID mutation alone or carrying disrupted IFN-gamma genes alone. Mice wi th gene disruptions of inducible nitric oxide synthetase or Fas/Fas ligand recovered normally from CP infection. The results indicate that mice unable to produce specific immune responses because of the SCID mutation require IFN-gamma to avoid death after infection with CP.