Environmental microbes and uveitis: is microbial exposure always bad?

The eye generally is considered to be an immune-privileged organ, but this notion is being increasingly challenged as ocular antigens can be expressed in the generative lymphoid organs, resulting in attainment of self-tolerance. What triggers a break in this tolerant state is a fundamental question in autoimmunity research. The general belief is that exposure to environmental microbes can break self-tolerance in genetically susceptible individuals, leading to the induction of autoimmune responses. The molecular mimicry hypothesis has been proposed as one major mechanistic, pathway through which microbes, by generating cross-reactive immune responses, can induce ocular damage of the kind that might occur in uveitis. However, our recent data suggest that exposure to microbial products containing mimicry epitopes for retinal antigens can potentially be beneficial to the host. In this review, we discuss the immune mechanisms with particular reference to the molecular mimicry hypothesis as it relates to immune-mediated uveitis.