Potential Interplay between Human Endogenous Retroviruses and Mycobacterium paratuberculosis in the Development of Type 1 Diabetes

Potential Interplay between Human Endogenous Retroviruses and Mycobacterium paratuberculosis in the Development of Type 1 Diabetes

The incidence of type 1 diabetes (T1D) has increased in recent decades in several industrialized countries, although this trend cannot be fully explained by genetic predisposition alone. The origin of Type 1 diabetes is still unknown, however different factors have been suggested as possible triggers for autoimmunity in susceptible people. It has become evident that environmental factors play a vital role in the progress of the disease, at least by modulating the expression of predisposing genetic factors in both positive and negative ways. This highlights the complex interplay between genetics and environment in the pathogenesis of T1D. Recent investigations suggest that human endogenous retroviruses (HERVs) might be involved in the development of some diseases. Numerous epigenetic mechanisms maintain the silence of most HERVs, however external factors including infections can lead to the reactivation of HERVs and possibly trigger health issues. Previous investigations have suggested that Mycobacterium paratuberculosis could represent an additional risk for Type 1 Diabetes, especially within the Sardinian population. The research presented here supports the connection through the increased immune response to specific protein fragments of MAP and HERVs in individuals at multiple stages of type 1 diabetes from different geographical backgrounds. A significant correlation between the immune response against MAP and HERVs peptides suggests potential cross-reactivity that might affect self-tolerance processes and result in autoimmunity. The findings indicate both external infections and internal reactivations have an impact in the development of Type 1 Diabetes, and that activation of HERV-W may be triggered by infectious agents like MAP.