Susceptibility to Cryptosporidium parvum infections in cytokine- and chemokine-receptor knockout mice.
To determine the role of cytokines and a chemokine receptor in the susceptibility to, and outcome of, infection, 4 different knockout mice (IL-4, IL-10, IL-12, and CCR5) were infected with Cryptosporidium parvum and monitored for infection intensity by collection of fecal pellets from individual mice. Because adult immunocompetent mice are refractory to infection, wild-type mice on the same background as the knockout mice (C57BL/6) were used as a negative control. No infection was detected over a 4-wk time period in IL-4, IL-10, and CCR5 knockout mice inoculated with 106 oocysts. IL-12 knockout mice inoculated with as little as 100 oocysts shed up to 10,000 oocysts/100 microl of feces on the peak infection day (day 8) and were able to fully recover by 2 wk after infection. IL-12 is an important inducer of IFN-gamma, which probably accounted for susceptibility to infection. Previous studies using IFN-gamma knockout mice have shown strain-related differences in infection intensity and outcome, with increased parasite loads and decreased survival among IFN-gamma knockout mice on a C57BL/6 background compared with those on a BALB/c background. Similar results were observed in IL-12 knockout mice on a BALB/c background, which exhibited little or no infection, despite higher levels of inoculation (10(6) oocysts/mouse).
Campbell
Lori D
LD
Department of Pediatrics, Emory University, Atlanta, Georgia 30033, USA.
Stewart
Julie N
JN
Mead
Jan R
JR
D000818:Animals; D003457:Cryptosporidiosis / Q000276:immunology*; D016785:Cryptosporidium parvum / Q000276:immunology* / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D005243:Feces / Q000469:parasitology; D005434:Flow Cytometry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D033661:Oocysts / Q000276:immunology / Q000378:metabolism; D019707:Receptors, Chemokine / Q000276:immunology* / Q000378:metabolism; D018121:Receptors, Cytokine / Q000276:immunology* / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
D019707:Receptors, Chemokine; D018121:Receptors, Cytokine