How rotavirus infection accelerates autoimmune diabetes in a mouse model

This is a cartoon of rotavirus particles (gray) containing their genome (red) on a background of real rotavirus particles imaged by electron microscopy (green). The rotavirus genome is detected by the immune response. This leads to increased activity of immune cells that possess the potential to destroy pancreatic islets. Credit: Barbara Coulson, et al.

A combination of genetic predisposition and environmental factors is believed to cause autoimmune (type 1) diabetes. A study published on March 27th in PLOS Pathogens gets at the mechanisms by which rotavirus infection contributes to autoimmune diabetes in a mouse model of the disease.

NOD (for non-obese diabetic) mice are prone to develop diabetes, and infection with rotavirus accelerates onset of the disease. Barbara Coulson and colleagues, from The University of Melbourne, Australia, tested the hypothesis that the virus does this by inducing "bystander activation".

Bystander activation assumes that a foreign intruder (in this case rotavirus) provokes a strong but non-specific activation of the immune system, and that this heightened state of activation "spills over" to a subset of specific that can recognize and attack not the viral intruder but some of the body's own cells, in this case the insulin-producing islet cells in the pancreas.

Indeed, the researchers found that when spleen cells from NOD mice encounter rotavirus, they activate two types of immune cells: antibody-producing B cells and so-called dendritic cells that are a key part of a coordinated immune response. They could show that this activation involves "unpacking" of the virus (thereby exposing its viral immune activators), as well as specific immune mediators of the host, including one called TLR7 and type 1 interferons.

Rotavirus activation of a specific dendritic cell type called was necessary for activation of another type of immune cells called T cells. These T cells can recognize and destroy islet cells and are ultimately responsible for . When activated, plasmacytoid produce very high levels of type 1 interferons, suggesting it has a specific role in mediating the bystander effect that connects rotavirus infection to accelerated diabetes.

Taken together, the results suggest that viral infection is capable of accelerating type 1 diabetes through an immune bystander effect and points to a number of key players—immune cells and immune modulators like interferon—that are linked to disease acceleration in the and worth investigating in humans. The authors conclude that, in particular, "the role of type 1 interferon signaling in diabetes acceleration following deserves further analysis."

More information: Pane JA, Webster NL, Coulson BS (2014) Rotavirus Activates Lymphocytes from Non-Obese Diabetic Mice by Triggering Toll-Like Receptor 7 Signaling and Interferon Production in Plasmacytoid Dendritic Cells. PLoS Pathog 10(3): e1003998. DOI: 10.1371/journal.ppat.1003998

add to favorites email to friend print save as pdf

Related Stories

Recommended for you

Student seeks to improve pneumonia vaccines

18 hours ago

Almost a million Americans fall ill with pneumonia each year. Nearly half of these cases require hospitalization, and 5-7 percent are fatal. Current vaccines provide protection against some strains of the ...

Seabed solution for cold sores

20 hours ago

The blue blood of abalone, a seabed delicacy could be used to combat common cold sores and related herpes virus following breakthrough research at the University of Sydney.

Better living through mitochondrial derived vesicles

Aug 19, 2014

(Medical Xpress)—As principal transformers of bacteria, organelles, synapses, and cells, vesicles might be said to be the stuff of life. One need look no further than the rapid rise to prominence of The ...

Zebrafish help to unravel Alzheimer's disease

Aug 19, 2014

New fundamental knowledge about the regulation of stem cells in the nerve tissue of zebrafish embryos results in surprising insights into neurodegenerative disease processes in the human brain. A new study by scientists at ...

User comments