UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

The role of antigen presenting cells in coxsackieviral-induced autoimmune diseases Richer, Martin Joseph


Susceptibility to autoimmune diseases is dictated by the interplay of genetic determinants and environmental factors including diet, toxins and infections. Viral infections have long been suspected to play a role in the etiology of several autoimmune disorders. In particular, coxsackieviruses are common human pathogens that have been linked to autoimmune myocarditis and type 1 diabetes (T1D). Evidence suggests that interactions between a pathogen and components of the innate immune system may influence the generation of a dysregulated adaptive response ultimately resulting in autoimmune disease development. Early recognition of viral infection is mediated by pattern recognition receptors (PRRs) expressed by a variety of cells including antigen presenting cells (APCs). PRR mediated recognition of an invading pathogen results in wide ranging functional consequences that serve to trigger innate antiviral mechanisms as well as the maturation of APCs and the activation of adaptive immune responses. As such, innate interactions between viruses and APCs likely represent a potential risk factor for the development of autoimmunity following infection. Here, I demonstrate that early protection from coxsackievirus infection is critically dependent on Toll-like receptor (TLR) 3 signaling on CD11b+CD11c- APCs. Interestingly, my work demonstrates that this same subset of APCs is central to the acceleration of T1D and that manipulation of the maturation and inflammatory status of CD11b+CD11c- APCs is sufficient to protect from coxsackievirus-induced autoimmune myocarditis and T1D. Protection from T1D is dependent on the reduction of costimulatory molecule expression, particularly CD40, on the surface of CD11b+CD11c- APCs which in turn increases the capacity of these APCs to induce protective regulatory T cells (Tregs) in the pancreas. Protection from autoimmune myocarditis is not dependent on Tregs and can be circumvented by activation of the TLR4 signaling pathway. Taken together, this work illustrates an important role for a particular subset of APCs that is critical for both early protection of the host as well as the induction of autoimmunity following infection with coxsackieviruses. This strongly suggests that CD11b+CD11c- APCs represent a potential therapeutic target for the prevention of viral-induced autoimmunity.

Item Media

Item Citations and Data


Attribution-NonCommercial-NoDerivatives 4.0 International