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Experimental Cryptosporidium parvum infections in immunosuppressed adult mice
1Department of Animal, Dairy and Veterinary Sciences, Utah State University, Logan 84322-5600.
Abstract:
Five strains of adult mice were immunosuppressed with the synthetic glucocorticosteroid dexamethasone (DEX), administered either orally or intraperitoneally. The strains of mice used were C57BL/6N, DBA/2N, CBA, C3H/HeN, and BALB/cAnN. All mice were evaluated for susceptibility to Cryptosporidium parvum after intragastric inoculation with 10(6) oocysts per mouse. The DBA/2N, CBA, C3H/HeN, and BALB/cAnN mice given 0.25 micrograms of DEX per g per day orally (the dose and route previously used to infect rats with C. parvum) failed to develop chronic infections. However, the C57BL/6N mice sustained light infections during the entire 28-day experiment. The five strains of mice were also administered DEX intraperitoneally at concentrations ranging from 62.5 to 500 micrograms/day. Only the C57BL/6N mice given DEX at 125 micrograms/day developed chronic infections which persisted over 10 weeks, suggesting that the genetic background of the mouse plays a role in determining susceptibility to cryptosporidosis following immunosuppression with DEX. We believe that the C57BL/6N mouse model will prove to be superior to other animal models for evaluating potential anticryptosporidial agents, as well as for elucidating the immunological defects that allow C. parvum to establish chronic infections, because of cost effectiveness and ease in maintenance, breeding, and handling. We also evaluated the C3H/HeJ/beige mouse (lacks natural killer cell activity) and the C57BL/6N mouse maintained on a low-protein diet to induce immunosuppression. Neither of these mice exhibited heavy cryptosporidial infections.
Insights
Genetic background influences mouse susceptibility to Cryptosporidium parvum infection after dexamethasone (DEX) immunosuppression. C57BL/6N mice are identified as a superior model for studying cryptosporidiosis and evaluating anticryptosporidial agents.
Area of Science:
- Immunology
- Infectious Diseases
- Animal Models
Background:
- Cryptosporidium parvum is an opportunistic parasite causing significant morbidity in immunocompromised individuals.
- Dexamethasone (DEX) is a synthetic glucocorticosteroid used to induce immunosuppression in animal models.
- Understanding host genetic factors influencing susceptibility to cryptosporidiosis is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the susceptibility of five different mouse strains to Cryptosporidium parvum following dexamethasone-induced immunosuppression.
- To identify a suitable mouse model for studying cryptosporidiosis and testing anticryptosporidial therapies.
Main Methods:
- Five strains of adult mice (C57BL/6N, DBA/2N, CBA, C3H/HeN, BALB/cAnN) were immunosuppressed with dexamethasone (DEX) via oral or intraperitoneal administration.
- Mice were inoculated intragastrically with 10(6) Cryptosporidium parvum oocysts.
- Susceptibility was assessed by monitoring infection chronicity over 28 days and up to 10 weeks.
Main Results:
- Only C57BL/6N mice developed chronic Cryptosporidium parvum infections, particularly when DEX was administered intraperitoneally at 125 micrograms/day.
- Other mouse strains (DBA/2N, CBA, C3H/HeN, BALB/cAnN) failed to develop chronic infections with oral DEX administration.
- C3H/HeJ/beige mice and C57BL/6N mice on a low-protein diet did not exhibit heavy infections, suggesting specific genetic or immune factors are key.
Conclusions:
- Mouse genetic background significantly influences susceptibility to cryptosporidiosis following dexamethasone-induced immunosuppression.
- The C57BL/6N mouse model is proposed as a superior, cost-effective, and manageable model for cryptosporidiosis research.
- This model can aid in evaluating anticryptosporidial agents and understanding the immunological basis of chronic infections.