Infections and autoimmunity--good or bad?

The relationship between infections and autoimmunity is complex. Current evidence indicates that microbes can initiate, enhance, or, conversely, abrogate autoimmunity. In this paper, we will review experimental examples illustrating mechanisms involved in these three scenarios. Microbial infections can act as environmental triggers inducing or promoting autoimmunity resulting in clinical manifestations of autoimmune disease in genetically predisposed individuals. However, increasing evidence suggests the opposite outcome, which is the prevention or amelioration of autoimmune processes following microbial encounters. These latter observations support conceptually the "hygiene hypothesis," suggesting that cleaner living conditions will lead to enhanced incidence of autoimmune disorders, asthma, and allergies. Because proof of concept in humans is difficult to obtain, we will discuss relevant animal model data in context with likely or proven human associations. Knowledge of mechanisms that underlie either positive or negative effects of infections on autoimmunity will facilitate exploration of molecular details for prospective clinical studies in the future.