Interferons induce an antiviral state in human pancreatic islet cells

Hultcrantz, Monica; Hühn, Michael; Wolf, Monika; Olsson, Anna-Karin; Jacobson, S.; Williams, Bryan R.G.; Korsgren, Olle; Flodström‐Tullberg, Malin

doi:10.1016/j.virol.2007.05.010

Cited by 83 publications

(86 citation statements)

References 58 publications

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“…Some enteroviruses, including the CVBs, are pancreatropic and can infect human beta cells in vitro, often with a detrimental outcome (e.g. [6,12]). Furthermore, experimental animal models have indicated that enterovirus infections can cause direct beta cell damage [13,14] and alter disease progression in the NOD mouse model [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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Aims/hypothesis Enterovirus (e.g. Coxsackie B virus serotypes [CVBs]) infections may be associated with development of type 1 diabetes. Studies conducted in several European countries have, however, shown an inverse correlation between the incidence of type 1 diabetes and the prevalence of enterovirus infections. These findings could in part be explained by an extension of the poliovirus hypothesis, suggesting that the absence of maternally transferred antibodies protecting offspring from early infection increases the risk for diabetes development. Experimental evidence supporting this hypothesis in type 1 diabetes is, however, lacking. As maternally transferred protection from infection is a crucial component of the extended poliovirus hypothesis, we here tested the hypothesis that previously infected females transfer protection against infection and diabetes to offspring.Methods The induction of CVB-specific maternal antibodies and transfer of protection from virus infection, replication and development of virus-induced diabetes to offspring was assessed using NOD and Socs1-transgenic NOD mice. Results Infected mice produced neutralising antibodies to CVB. Offspring from infected females were positive for neutralising antibodies and were strongly protected from both infection and experimental diabetes. Conclusions/interpretation Our study shows that maternally transferred antibodies protect offspring from enterovirus infection and virus-induced diabetes. This suggests that the absence of maternally provided protection increases the risk for severe outcomes after an enterovirus infection in offspring. Moreover, our findings may have implications for the design of prospective studies aimed at investigating the possible role of enterovirus infections in the aetiology of human type 1 diabetes.

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Section: Introductionmentioning

confidence: 99%

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

et al. 2013

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“…Human pancreatic islets infected with the Coxsackie B5 virus or exposed to IFN-a or IFN-g + IL-1b exhibit increased expression of Toll-like receptor 3 (TLR3) and RLHs (RIG-1 and IFIH1) (32,33). Both intracellular and extracellular dsRNA may bind to TLR3 and trigger the production of proinflammatory cytokines and chemokines, resulting in beta-cell apoptosis by means of the activation of key transcription factors: nuclear factor-kappa B (NF-κB) and IFN-regulatory factor 3 (IRF-3) (34)(35)(36).…”

Section: The Role Of Pattern Recognition Receptors (Prrs) In the Respmentioning

confidence: 99%

“…The human IFIH1 gene is located on chromosome 2 (region 2q24.3), contains 16 exons ( Figure 3) and encodes a 1,025-amino acid protein with a molecular mass of 116.7 KDa (42,46). This helicase is expressed at low levels in a wide range of tissues, including pancreatic beta-cells, but is expressed at relatively high concentrations in immune cells (32,46). At the transcriptional level, IFIH1 expression is induced by IFN-I, retinoic acid, and dsRNA (42).…”

Section: The Interferon Induced With Helicase C Domain 1 (Ifih1) Recementioning

confidence: 99%

“…Hultcrantz and cols. (32) showed that, in human pancreatic islets, IFN-induced antiviral defenses provide a powerful protective mechanism against replication of coxsackieviruses. Treatment with IFN-a is known to increase gene expression of the chemokine CXCL10 in human islets (32).…”

Section: Hühn and Cols (47) Found That Ifih1mentioning

confidence: 99%

“…(32) showed that, in human pancreatic islets, IFN-induced antiviral defenses provide a powerful protective mechanism against replication of coxsackieviruses. Treatment with IFN-a is known to increase gene expression of the chemokine CXCL10 in human islets (32). This chemokine, when produced during infection, leads to T-cell recruitment to the islet site and appears to play a key role in host defense against islettropic viruses in individuals susceptible to T1DM (32).…”

Section: Hühn and Cols (47) Found That Ifih1mentioning

confidence: 99%

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The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus

Bouças

Oliveira

Canani

et al. 2013

Arq Bras Endocrinol Metab

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Type 1 diabetes mellitus (T1DM) is a chronic, progressive, autoimmune disease characterized by metabolic decompensation frequently leading to dehydration and ketoacidosis. Viral pathogens seem to play a major role in triggering the autoimmune destruction that leads to the development of T1DM. Among several viral strains investigated so far, enteroviruses have been consistently associated with T1DM in humans. One of the mediators of viral damage is the double-stranded RNA (dsRNA) generated during replication and transcription of viral RNA and DNA. The IFIH1 gene encodes a cytoplasmic receptor of the pattern-recognition receptors (PRRs) family that recognizes dsRNA, playing a role in the innate immune response triggered by viral infection. Binding of dsRNA to this PRR triggers the release of proinflammatory cytokines, such as interferons (IFNs), which exhibit potent antiviral activity, protecting uninfected cells and inducing apoptosis of infected cells. The IFIH1 gene appears to play a major role in the development of some autoimmune diseases, and it is, therefore, a candidate gene for T1DM. Within this context, the objective of the present review was to address the role of IFIH1 in the development of T1DM. Arq Bras Endocrinol Metab. 2013;57(9):667-76 Keywords Autoimmunity; type 1 diabetes mellitus; viral infection; IFIH1 RESUMO O diabetes melito tipo 1 (T1DM) é uma doença autoimune crônica e progressiva caracterizada por descompensações metabólicas frequentemente acompanhadas por desidratação e cetoacidose. Os agentes virais parecem ter um papel importante no desencadeamento da destruição autoimune que leva ao desenvolvimento do T1DM. Entre as cepas virais estudadas até agora, a família dos enterovírus foi consistentemente associada ao surgimento da doença em humanos. Um dos mediadores do dano viral é o RNA fita dupla (RNAfd) gerado durante a replicação e transcrição de RNA e DNA viral. O gene IFIH1 codifica um receptor citoplasmático pertencente à família dos pattern-recognition receptors (PRRs) que reconhece o RNAfd, tendo um papel importante na resposta imune inata desencadeada por infecção viral. A ligação do RNAfd a essa PRR desencadeia a liberação de citocinas pró-inflamatórias como interferons (IFNs), os quais exibem uma potente ação antiviral e têm como objetivo proteger as células não infectadas e induzir apoptose naquelas já contaminadas. O gene IFIH1 parece ter uma participação importante no desenvolvimento de algumas doenças autoimunes. Por isso, esse gene é um candidato ao desenvolvimento do T1DM. Dentro desse contexto, o objetivo da presente revisão foi abordar o papel do IFIH1 no desenvolvimento do T1DM. Arq Bras Endocrinol Metab.2013;57(9):667-76 Descritores Autoimunidade; diabetes melito tipo 1; infecção viral; IFIH1

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Fulminant type 1 diabetes: A comprehensive review of an autoimmune condition

Luo

et al. 2020

Diabetes Metabolism Res

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Summary Fulminant type 1 diabetes (FT1D) is a subset of type 1 diabetes characterized by extremely rapid pancreatic β‐cell destruction with aggressive progression of hyperglycaemia and ketoacidosis. It was initially classified as idiopathic type 1 diabetes due to the absence of autoimmune markers. However, subsequent studies provide evidences supporting the involvement of autoimmunity in rapid β‐cell loss in FT1D pathogenesis, which are crucial for FT1D being an autoimmune disease. This article highlights the role of immunological aspects in FT1D according to the autoimmune‐associated genetic background, viral infection, innate immunity, adaptive immunity, and pancreas histology.

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Interferons induce an antiviral state in human pancreatic islet cells

Cited by 83 publications

References 58 publications

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

Previous maternal infection protects offspring from enterovirus infection and prevents experimental diabetes development in mice

The role of interferon induced with helicase C domain 1 (IFIH1) in the development of type 1 diabetes mellitus

Fulminant type 1 diabetes: A comprehensive review of an autoimmune condition

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