Pane Jessica A, Coulson Barbara S
Department of Microbiology and Immunology, The University of Melbourne at the Peter Doherty Institute for Infection and Immunity, 792 Elizabeth Street, Melbourne, VIC, 3010, Australia.
Diabetologia. 2015 Jun;58(6):1149-59. doi: 10.1007/s00125-015-3562-3. Epub 2015 Mar 21.
Viruses are considered to be potential key modulators of type 1 diabetes mellitus, with several possible mechanisms proposed for their modes of action. Here we discuss the evidence for virus involvement, including pancreatic infection and the induction of T cell-mediated molecular mimicry. A particular focus of this review is the further possibility that virus infection triggers bystander activation of pre-existing autoreactive lymphocytes. In this scenario, the virus triggers dendritic cell maturation and proinflammatory cytokine secretion by engaging pattern recognition receptors. These proinflammatory cytokines provoke bystander autoreactive lymphocyte activation in the presence of cognate autoantigen, which leads to enhanced beta cell destruction. Importantly, this mechanism does not necessarily involve pancreatic virus infection, and its virally non-specific nature suggests that it might represent a means commonly employed by multiple viruses. The ability of viruses specifically associated with type 1 diabetes, including group B coxsackievirus, rotavirus and influenza A virus, to induce these responses is also examined. The elucidation of a mechanism shared amongst several viruses for accelerating progression to type 1 diabetes would facilitate the identification of important targets for disease intervention.
病毒被认为是1型糖尿病潜在的关键调节因子，针对其作用模式已提出了几种可能的机制。在此，我们讨论病毒参与其中的证据，包括胰腺感染以及T细胞介导的分子模拟的诱导。本综述的一个特别关注点是病毒感染引发预先存在的自身反应性淋巴细胞旁观者激活的进一步可能性。在这种情况下，病毒通过激活模式识别受体来触发树突状细胞成熟和促炎细胞因子分泌。这些促炎细胞因子在存在同源自身抗原的情况下引发旁观者自身反应性淋巴细胞激活，进而导致β细胞破坏加剧。重要的是，这一机制不一定涉及胰腺病毒感染，其病毒非特异性性质表明它可能是多种病毒常用的一种手段。我们还研究了与1型糖尿病特异性相关的病毒，包括B组柯萨奇病毒、轮状病毒和甲型流感病毒诱导这些反应的能力。阐明几种病毒共同的加速1型糖尿病进展的机制将有助于确定疾病干预的重要靶点。
