The impact of infection on the incidence of autoimmune disease.

Falling infection rates in the developed world are being matched by a rapidly rising incidence of allergic and autoimmune diseases. This review explores the hypothesis that there is a causal link between these phenomena and that infections can prevent the onset of autoimmune disease. The hypothesis is discussed with particular reference to Type I diabetes in the NOD mouse and the ability of the helminth infection Schistosoma mansoni to prevent its onset. The article addresses the possible mechanisms that underly this protection. The effects of protective pathogen-derived agents on key cells of the innate immune system such as dendritic cells are distinct and include the production of anti-inflammatory cytokines such as IL-10. The most likely mechanisms by which these innate changes prevent the subsequent adaptive autoimmune destruction are: (1) the production of systemically high levels of cytokines that oppose the production of cytokines that drive the autoimmune process - possibly via the action of natural killer T (NKT) cells (2) the induction of regulatory T cells that inhibit the action of autoreactive cells and (3) the production of pathogen-specific T cells that are not autoreactive and compete with autoreactive cells for survival signals such as cytokines and T cell receptor ligation.