The basis for the resistance of the female and the susceptibility of the male ICR Swiss mouse to the diabetogenicity of the D variant of encephalomyocarditis virus (EMCV-D) is unknown. This pattern of disease resistance and susceptibility can be reversed if females are treated with testosterone and males are treated with estrogen before virus infection. As a possible explanation for this sex difference in disease development, differences in early antiviral host responses were explored. Cellular antiviral resistance mechanisms operative early in virus infection were evaluated in ICR Swiss mice of both sexes after intraperitoneal infection with virus. No differences were seen in splenic natural killer (NK) cell responses of male and female mice during the 1st wk of infection, during which only the males became diabetic. Depletion of NK cell activity with rabbit anti-asialo GM1 serum did not render the infected ICR Swiss female susceptible to virus-induced diabetes. Treatment of ICR Swiss mice with type I carrageenan to compromise macrophage function rendered the female susceptible to diabetes after infection with EMCV-D but made only the male susceptible to diabetes by the usually avirulent interferon-inducing EMCV-B. Concanavalin A and recombinant interleukin 2, inducers of immune interferon, which in turn primes macrophages for activation and induces their expression of la antigens, protected the ICR Swiss male against the diabetogenic effects of EMCV-D. Interleukin 2 enhanced the male's capacity to exhibit an increase in the expression of la antigen by peritoneal exudate cells 1 day after infection with EMCV-D to a level seen in disease-resistant females. These results suggest that the more responsive macrophage system of the female is important in the innate resistance of the ICR Swiss female to virus-induced diabetes and, conversely, the less responsive macrophage system of the male contributes to his susceptibility to diabetes induction by EMCV-D and by EMCV-B after impairment of macrophage function.
Impaired Cytokine Response in Male ICR Swiss Mice After Infection With D Variant of Encephalomyocarditis Virus
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Nancy J Bigley, Roy A Blay, Randall A Smith; Impaired Cytokine Response in Male ICR Swiss Mice After Infection With D Variant of Encephalomyocarditis Virus. Diabetes 1 December 1987; 36 (12): 1408–1413. https://doi.org/10.2337/diab.36.12.1408
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