From infection to autoimmunity

We have investigated two models of virally-induced autoimmune myocarditis i n mice using widely different infectious agents. Infection of susceptible B ALB/c mice with either Coxsackievirus or murine cytomegalovirus results in the development of acute myocarditis from day 7-14 after infection, and chr onic myocarditis from day 28 onwards. The chronic phase of myocarditis is a ssociated with mononuclear infiltration of the myocardium and the productio n of autoantibodies to cardiac myosin, although infectious virus cannot be detected past day 14 of infection. T cells and autoantibodies have been sho wn to be important for the development of autoimmune myocarditis. Many rese archers have investigated the role of molecular mimicry in the development of myocarditis after viral infection. This review explores the 'adjuvant' e ffect of infection on the innate immune response and how this determines th e progression to autoimmune disease. We show that NK cells protect against the development of disease, while complement and complement receptors are i nvolved in the development of autoimmune myocarditis induced by inoculation with virus or cardiac myosin, respectively. Our results suggest that the i nnate immune response to viral and self-antigens may determine whether susc eptible strains of mice progress to chronic autoimmune disease. These findi ngs have broad implications for understanding the role of infection in indu cing autoimmune disease. (C) 2001 Academic Press.