Interferon-gamma is required for innate immunity to Cryptosporidium parvum in mice.
Although CD4 T cells are required for recovery from cryptosporidial infection, mice with severe combined immunodeficiency (SCID) remain infected for long periods without ill effect. In contrast, mice whose ability to use interferon(IFN)-gamma is impaired, by neutralization or gene knockout, experience heavy cryptosporidial infection that may lead to death. To determine whether the innate immunity of SCID mice to Cryptosporidium parvum (CP) requires IFN-gamma, doubly immunodeficient C57BL/6 SCID-IFN-gamma knockout mice were bred. These mice experienced heavy CP infections of the gut; a significantly greater number became moribund or died, compared with mice carrying the SCID mutation alone or carrying disrupted IFN-gamma genes alone. Mice with 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.
Hayward
A R
AR
Departments of Immunology and Pediatrics and the Barbara Davis Childhood Diabetes Center, University of Colorado School of Medicine, Denver, CO 80262, USA. anthony.hayward@uchsc.edu
Chmura
K
K
Cosyns
M
M
D000818:Animals; D003457:Cryptosporidiosis / Q000150:complications / Q000276:immunology*; D016785:Cryptosporidium parvum; D053222:Fas Ligand Protein; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000502:physiology*; D007583:Jejunum / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D016511:Severe Combined Immunodeficiency / Q000150:complications / Q000276:immunology; D019014:fas Receptor / Q000235:genetics
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse