Innate Immunity of Human Pancreatic Islets Infected with Different Enterovirus Types

Chapter

Abstract

Human enterovirus (HEV) infections are believed to be an environmental factor in the pathogenesis of type 1 diabetes pathogenesis, but the exact mechanism behind beta-cell death still remains unclear. Accumulating evidence suggests that viral induction of cytokines and chemokines promoting insulitis could be the link between virus infection and type 1 diabetes. When isolated human pancreatic islets are infected with HEV, IP-10 and MCP-1 are secreted from the islets. HEV infection of human islets induces many genes involved in the innate immune response or sensing viral dsRNA such as IL-6, IL-8, RANTES and INF-b, TLR3 and MDA5. If these proteins were expressed in the pancreas, they would promote b-cell death, directly or indirectly by attracting immune cells. Enterovirus-positive pancreatic sections from recent-onset type 1 diabetes cases also expressed the IP10 chemokine. T cells infiltrating the same areas expressed CXCR3, the IP10 receptor. In pancreatic sections from type 1 diabetes patients at onset stained positive for HEV protein 1 IP-10 was detected and, in addition, CCXCR3 was expressed on islet infiltrating was T-cells. These findings support the idea of HEV infection as a trigger of the immune-mediated beta-cell destruction and also suggest a possible mechanism for HEV-induced type 1 diabetes. The induction and secretion of the chemokine IP-10 with a prominent role in the induction of insulitis might be one of the key targets for immune intervention in this group of patients.

Keywords

Estrogen Interferon Kato Nicotinamide 

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Women’s and Children’s HealthUppsala University, Akademiska HospitalUppsalaSweden

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