| Clostridium piliforme infections are commonly subclinical in laboratory rats and mice, but little is known about the effects of silent infections on research animals or on investigations that utilize infected animals, or of the role of the immune system in control of this disease. Susceptible DBA/2 and resistant C57BL/6 mice were depleted of neutrophils, natural killer (NK) cells, macrophages, IL-6, or IL-12 and inoculated iv with toxic H1 C. piliforme. Depletion of neutrophils, natural killer cells, IL-6 or IL-12 in weanling mice increased severity of disease at 3 days post-C. piliforme inoculation. NK cells and IL-12 appear to mediate strain susceptibility to Tyzzer's disease. Macrophage depletion did not alter the course of infection in either mouse strain. In additional studies to assess effects of subclinical C. piliforme infections on research mice, juvenile DBA/2 and C57BL/6 mice were inoculated with either H1 or nontoxic (M1) C. piliforme. Evaluation of samples at 0 (pre-inoculation), 1, 3, 7, 14, and 28 days documented that hepatic mRNA expression and serum levels for tumor necrosis factor alpha (TNF), interferon gamma (IFN), IL-6 and IL-12 were elevated by both C. piliforme isolates and in both strains of mice. TNF and IL-12 perturbations persisted for at least 28 days. These findings suggest that differences in cellular and early Th1 type immune response may mediate murine strain susceptibility to C. piliforme. |