Interaction of enterovirus infection and cow's milk‐based formula nutrition in type 1 diabetes‐associated autoimmunity

Lempainen, Johanna; Tauriainen, Sisko; Vaarala, Outi; Mäkelä, Miia; Honkanen, Hanna; Marttila, Jane; Veijola, Riitta; Simell, Olli; Hyöty, Heikki; Knip, Mikael; Ilonen, Jorma

doi:10.1002/dmrr.1294

Cited by 44 publications

(40 citation statements)

References 47 publications

(51 reference statements)

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“…RRV acceleration of diabetes and RRV-specific serum antibody responses in NOD8.3 mice each depended on virus dose and required virus replication, providing further evidence that diabetes acceleration relates to antibody responses. Although childhood rotavirus infection frequently induces specific intestinal IgA without detectable serum antibody [31], the childhood diabetes studies identified rotavirus infections by seroconversion [10,11]. Our mouse data indicate that these infections would be more likely to modulate childhood diabetes.…”

Section: Discussionmentioning

confidence: 76%

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Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

et al. 2012

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Aims/hypothesis Rotavirus infection in at-risk children correlates with production of serum autoantibodies indicative of type 1 diabetes progression. Oral infection with rhesus monkey rotavirus (RRV) accelerates diabetes onset in mice. This relates to their rotavirus-specific serum antibody titre and local pro-inflammatory cytokine induction without pancreatic infection. Our aim was to further investigate the roles of serum antibodies and viral extra-intestinal spread in diabetes acceleration by rotavirus. Methods Rotavirus-specific serum antibody production was detected by ELISA in diabetes-prone mice given either inactivated or low-dose RRV, in relation to their diabetes development. Serum anti-rotavirus antibody titres and infectious virus in lymph nodes were measured in mice given RRV or porcine rotavirus CRW-8. In lymph node cells, rotavirus antigen presence and immune activation were determined by flow cytometry, in conjunction with cytokine mRNA levels. Results Acceleration of diabetes by RRV required virus replication, which correlated with antibody presence. CRW-8 induced similar specific total immunoglobulin and IgA titres to those induced by RRV, but did not accelerate diabetes. RRV alone elicited specific serum IgG antibodies with a T helper (Th)1 bias, spread to regional lymph nodes and activated antigen-presenting cells at these sites. RRV increased Th1-specific cytokine expression in pancreatic lymph nodes. Diabetes onset was more rapid in the RRVinfected mice with the greater Th1 bias. Conclusions/interpretation Acceleration of murine diabetes by rotavirus is virus strain-specific and associated with virus spread to regional lymph nodes, activation of antigenpresenting cells at these sites and induction of a Th1-dominated antibody and cytokine response.

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Section: Discussionmentioning

confidence: 76%

“…The gastrointestinal pathogen rotavirus is associated with exacerbations in islet autoantibodies in children genetically at risk of type 1 diabetes [10,11]. Rotavirus infection in atrisk children also relates to increased bovine insulin antibodies, possibly due to enhanced intestinal permeability and dietary insulin uptake [12].…”

Section: Introductionmentioning

confidence: 99%

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

et al. 2012

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“…However, a more recent study suggests that consumption of cows' milk very early in life may trigger type 1 diabetes if it is accompanied by exposure to enterovirus infections in early life (Lempainen et al 2012).…”

Section: Diabetesmentioning

confidence: 99%

Animal (De)liberation: Should the Consumption of Animal Products Be Banned?

Deckers

2016

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“…In an Australian study of children with a high genetic risk of developing type 1 diabetes, a temporal correlation was observed between serum anti-rotavirus antibodies and the presence of antibodies against the islet autoantigens insulin, GAD65 and IA-2 [6]. More recently, rotavirus infection before 6 months of age in combination with exposure to cow's milk was also associated with an increase in autoantibodies to GAD65 [97].…”

Section: How Might Bystander Lymphocyte Activation Contribute To Diabmentioning

confidence: 97%

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes

Pane

Coulson

2015

Diabetologia

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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.

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Interaction of enterovirus infection and cow's milk‐based formula nutrition in type 1 diabetes‐associated autoimmunity

Cited by 44 publications

References 47 publications

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

Rotavirus acceleration of murine type 1 diabetes is associated with a T helper 1-dependent specific serum antibody response and virus effects in regional lymph nodes

Animal (De)liberation: Should the Consumption of Animal Products Be Banned?

Lessons from the mouse: potential contribution of bystander lymphocyte activation by viruses to human type 1 diabetes

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