Trypanosoma brucei rhodesiense Infection in Mice Prevents Virus-Induced Diabetes: Possible Role of Interferon and Immunological Mechanisms

Abstract

B1O.BR, DBA/2, and BALB/c by J mice were infected with Trypanosoma brucei rhodesiense (Lou Tat clone 1). Subsequent infection with the D variant of encephalomyocarditis virus (EMC-D) resulted in no diabetes or encephalitis, even in the susceptible DBA/2 and BALB/c by J strains. Low levels of circulating interferon (IFN) were detected in trypanosome-infected mice at the time of EMC-D infection. All strains were severely immunosuppressed as a result of trypanosome infection, as evidenced by decreased virus-specific neutralizing antibody liters, compared to virus-infected controls. We attempted to simulate some aspects of T.b. rhodesiense infection in B1O.BR mice by pretreating mice with cyclophosphamide and IFN prior to EMC-D infection. Immunosuppression by cyclophosphamide greatly enhanced the pathogenesis of EMC-D, while IFN protected against the diabetogenic effect of this virus. Our results indicate that: (i) T. b. rhodesiense infection inhibited EMC-D-induced diabetes, (ii) this inhibition was not due solely to the immunosuppression generated by the trypanosome infection, and (iii) IFN generated by the trypanosome infection could play some protective role in the inhibition of EMC-D-induced diabetes by trypanosome infection.