Interference of natural mouse hepatitis virus infection with cytokine production and susceptibility to Trypanosoma cruzi

Mouse hepatitis virus (MHV) infection can have a pronounced impact on sever al investigation areas. Reports on natural MHV outbreaks are rare and most studies have been conducted by deliberately infecting mice with MHV laborat ory strains that cause moderate to severe disturbances to the immune system . We have investigated the effects of a natural acute outbreak of MHV in ou r otherwise specific-pathogen-free (SPF) inbred mouse colonies, and of enzo otic chronic MHV infection on cytokine production and resistance to the int racellular pathogen Trypanosoma cruzi. We found that BALB/c and/or C57BL/6 SPF mice that had been injected with T. cruzi blood trypomastigotes from re cently MHV(-)contaminated (MHV+) mice developed significantly higher parasi te blood counts, accelerated death, and showed higher IL-10 production by s pleen cells than their counterparts whose T. cruzi inoculum was derived fro m MHV-negative (MHV-) donors. Interferon-gamma (IFN-gamma) production by MH V+ and MHV- mice was not significantly different. In contrast, T. cruzi inf ection of chronically MHV-infected mice did not result in major changes in the course of infection when compared with that observed in mice from MHV- colonies, although a trend to higher parasitaemia levels was observed in BA LB/c MHV+ mice. Nevertheless, both BALB/c and C57BL/6 T. cnuzi-infected MHV + mice had diminished IFN-gamma production to parasite-antigen stimulation in comparison with similarly infected MHV- mice. Interleukin-10 (IL-10) pro duction levels by spleen cells did not differ between chronic MHV+ and MHV- mice, but IFN-gamma neutralization by monoclonal antibody treatment of ant i-CD3-stimulated spleen cell cultures showed higher levels of IL-10 synthes is in MHV+ BALB/c mice.