Innate Immunity of Human Pancreatic Islets Infected with Different Enterovirus Types



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.


Innate Immune Response Human Islet CXCL10 Level Human Pancreatic Islet Pancreatic Section 
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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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