Pathogenesis of type 1 diabetes mellitus: interplay between enterovirus and host

• Published in: Nature reviews. Endocrinology Vol. 6; no. 5; pp. 279 - 289
• Main Authors: Hober, Didier, Sauter, Pierre
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2010; Nature Publishing Group
• Subjects: 631/326/596/2555; 692/699/2743/1313/1418; Adaptive Immunity; Diabetes; Diabetes Mellitus, Type 1 - etiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - virology; Diagnosis; Disease; Endocrinology; Enterovirus - physiology; Enterovirus Infections - complications; Enteroviruses; Epidemiology; Genetic aspects; Health aspects; Humans; Hygiene; Hypotheses; Immune system; Immune Tolerance; Immunity, Innate; Infections; Insulin-Secreting Cells - physiology; Medicine; Medicine & Public Health; Molecular Mimicry; Pancreas; Pancreas - virology; Pathogenesis; Pathogens; Proteins; review-article; Risk factors; Type 1 diabetes; Viral infections; Viruses; France
• ISSN: 1759-5029; 1759-5037
• DOI: 10.1038/nrendo.2010.27

Enteroviruses are believed to contribute to the pathogenesis of type 1 diabetes mellitus. This Review discusses the interplay between infection with enteroviruses, the immune system and host genes, as an improved knowledge of the mechanisms involved could uncover preventive strategies for type 1 diabetes mellitus. Enteroviruses are believed to contribute to the pathogenesis of type 1 diabetes mellitus (T1DM). In this Review, the interplay between infection with enteroviruses, the immune system and host genes is discussed. Data from retrospective and prospective epidemiological studies strongly suggest the involvement of enteroviruses, such as coxsackievirus B, in the development of T1DM. Enteroviral RNA and/or proteins can be detected in tissues of patients with T1DM. Isolation of coxsackievirus B4 from the pancreas of patients with T1DM or the presence of enteroviral components in their islets strengthens the hypothesis of a relationship between the virus and the disease. Enteroviruses can play a part in the early phase of T1DM through the infection of β cells and the activation of innate immunity and inflammation. In contrast with its antiviral role, virus-induced interferon α can be deleterious, acting as an initiator of the autoimmunity directed against β cells. Enteroviruses, through persistent and/or successive infections, can interact with the adaptive immune system. Host genes, such as IFIH1 , that influence susceptibility to T1DM are associated with antiviral activities. An increased activity of the IFIH1 protein may promote the development of T1DM. An improved knowledge of the pathogenic mechanisms of enterovirus infections should help to uncover preventive strategies for T1DM. Key Points Enteroviruses have been detected in blood, gut and pancreas of patients with type 1 diabetes mellitus (T1DM) Enteroviruses act in the early phase of T1DM; interaction with the innate immune system and inflammatory mediators might induce and amplify the immune assault against pancreatic β cells By interaction with the adaptive immune system, enteroviruses play a part in the pathogenesis of T1DM through mechanisms that are not mutually exclusive: molecular mimicry, bystander activation, and disturbance of tolerance Enteroviruses interact with the adaptive immune system, which may also have a role in the pathogenesis of T1DM because antiviral antibodies are able to enhance the infection of monocytes or macrophages Enteroviruses acting through antiviral effectors—especially the pool of cytotoxic T lymphocytes enriched in the course of successive infections—may damage infected β cells and contribute to the release of self-antigens Genes that encode proteins with antiviral activities promote T1DM, and viral infections together with type 1 interferons can contribute to the development of the disease