The considerable prevalence of disease-discordant pairs among monozygotic twins underscores the pivotal role of environmental factors in the development of autoimmune diseases. Initial efforts were focused on identifying triggering factors, which have been found to include infections in animal models. For instance, the Coxsackie B4 virus has been linked to type I diabetes, while the encephalomyocarditis virus is associated with autoimmune myositis. In these models, viruses are thought to increase the immunogenicity of autoantigens by inducing local inflammation. In addition, there are cases of mimicry between microbial and human antigens. For instance, the induction of Guillaine-Barre syndrome in rabbits through immunization with a peptide derived from Campylobacter jejuni is explained by the similarity between C. jejuni antigens and peripheral nerve axonal antigens. In other models, chemical modification of autoantigens triggers autoimmune responses, such as in the case of iodine-induced autoimmune thyroiditis. Although these mechanisms have limited clinical counterparts, unknown viruses may be responsible for several chronic autoimmune diseases, including type I diabetes and multiple sclerosis. However, infections can also offer protection against autoimmune diseases. Western countries are currently witnessing a disturbing increase in the incidence of immune disorders, including autoimmune and allergic diseases, inflammatory bowel diseases, and some lymphocyte malignancies. This increase is believed to be linked to the improved socio-economic status of these countries, which raises the question of the causal relationship and the nature of the link. The hygiene hypothesis, which posits that the decrease in infections observed over the last three decades is the main cause of the rise in immune disorders, is supported by epidemiological and clinical data. This hypothesis does not rule out the possibility of a specific etiological role for certain pathogens in some immune disorders, such as inflammatory bowel diseases. Even in these cases, infections may still have a non-specific protective effect. Numerous questions remain regarding the mechanisms of protection and the nature of infectious agents that confer protection. Four orders of mechanisms are being explored, including antigenic competition and immunoregulation. The former hypothesis proposes that immune responses against pathogens compete with autoimmune and allergic responses, while the latter suggests that infectious agents stimulate various regulatory cells whose effects extend to other specificities. Toll receptors and TIM proteins present in Th cells may also play a role. The final proof of principle will be derived from therapeutic trials, where immune disorders will be prevented or cured using products derived from protective infectious agents. Several experimental data are already available in various models, with preliminary results in atopic dermatitis using bacterial extracts and probiotics.
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