Immunology in the Clinic Review Series: Focus on type 1 diabetes and viruses: the innate immune response to enteroviruses and its possible role in regulating type 1 diabetes

Department of Medicine HS, The Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
Clinical & Experimental Immunology (Impact Factor: 3.04). 04/2012; 168(1):30-8. DOI: 10.1111/j.1365-2249.2011.04557.x
Source: PubMed


Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy.
Type 1 diabetes (T1D) is an autoimmune disease arising as a consequence of a misdirected T cell response to the pancreatic beta cell. In recent years, there has been a growing interest in the innate immune system as a regulator of disease development. Genome-wide association studies have identified diabetes-associated polymorphisms in genes encoding proteins with functions related to the innate immune response. Moreover, enteroviruses, known to activate a strong innate immune response, have been implicated in the disease pathogenesis. In this review, we discuss the innate immune response elicited by enteroviruses and how this response may regulate T1D development.

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    • "Host immune response can modulate the course of enterovirus infection. In addition to the adaptive immune system, the innate immune system seems to be important [Curiel et al., 1998; Kemball et al., 2010; Lind et al., 2012]. Innate immune responses protect against the invading virus and tailor the complex networks, which modulate the anti-viral adaptive immune responses, and virus-induced inflammation. "
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    ABSTRACT: Enterovirus infections are usually mild but can also cause severe illnesses and play a role in chronic diseases, such as cardiomyopathies and type 1 diabetes. Host response to the invading virus can markedly modulate the course of the infection, and this response varies between individuals due to the polymorphism of immune response genes. However, it is currently not known if virus strains also differ in their ability to stimulate the host immune system. Coxsackievirus B1 (CBV1) causes severe epidemics in young infants and it has recently been connected with type 1 diabetes in seroepidemiological studies. This study evaluated the ability of different field isolates of CBV1 to induce innate immune responses in PBMCs. CBV1 strains differed markedly in their capacity to induce innate immune responses. Out of the 18 tested CBV1 strains two induced exceptionally strong alpha interferon (IFN-α) response in PBMC cultures. The responding cell type was found to be the plasmacytoid dendritic cell. Such a strong innate immune response was accompanied by an up-regulation of several other immune response genes and secretion of cytokines, which modulate inflammation, and adaptive immune responses. These results suggest that enterovirus-induced immune activation depends on the virus strain. It is possible that the immunotype of the virus modulates the course of the infection and plays a role in the pathogenesis of chronic immune-mediated enterovirus diseases. J. Med. Virol. © 2014 Wiley Periodicals, Inc.
    Full-text · Article · Aug 2014 · Journal of Medical Virology
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    ABSTRACT: The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. The mechanisms leading to the disease involve complex interactions between the virus, host target tissue (pancreas) and the immune system. The following article is intended as a review of several recent information of the topic based on human studies that try to establish a connection between a viral infection and Type 1 diabetes. Through understanding better this association and it's implications in the onset of T1D potential new ways of prevention and treatment may emerge.
    No preview · Article · Jan 2012
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    ABSTRACT: OTHER THEMES PUBLISHED IN THIS IMMUNOLOGY IN THE CLINIC REVIEW SERIES Metabolic diseases, host responses, cancer, autoinflammatory diseases, allergy. Convincing evidence now indicates that viruses are associated with type 1 diabetes (T1D) development and progression. Human enteroviruses (HEV) have emerged as prime suspects, based on detection frequencies around clinical onset in patients and their ability to rapidly hyperglycaemia trigger in the non-obese diabetic (NOD) mouse. Whether or not HEV can truly cause islet autoimmunity or, rather, act by accelerating ongoing insulitis remains a matter of debate. In view of the disease's globally rising incidence it is hypothesized that improved hygiene standards may reduce the immune system's ability to appropriately respond to viral infections. Arguments in favour of and against viral infections as major aetiological factors in T1D will be discussed in conjunction with potential pathological scenarios. More profound insights into the intricate relationship between viruses and their autoimmunity-prone host may lead ultimately to opportunities for early intervention through immune modulation or vaccination.
    Preview · Article · Apr 2012 · Clinical & Experimental Immunology
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