Celiac disease (CeD) is a complex immune mediated disorder that is triggered by abnormal immune responses to the dietary protein gluten, which is found in grains like wheat, barley, and rye. Normally, immune tolerance to dietary proteins prevents inflammatory immune responses from developing. However, in those with CeD, the presence of HLA susceptibility genes plus unknown environmental or immune triggers lead to a pro-inflammatory Th1 response towards gluten proteins. While gluten exposure and genetic risk are both required for CeD, only a proportion of genetically susceptible individuals will go on to develop the disease, highlighting a critical role of environmental modifiers. Epidemiological studies have suggested a link between infections or a dysbiotic microbiota and CeD, but mechanistic studies and experimental data to support these associations are lacking. Moreover, the events that lead to the loss of tolerance to these innocuous dietary proteins in the gut, like gluten, are not well understood.
A new study published in Science by Bouziat and colleagues show that reovirus, which are mild or clinically silent viruses that infect humans frequently over the course of a lifetime, can break tolerance to dietary proteins and may constitute an environmental modifier for CeD development. The collection of viruses within the body, known as the virome, is an often forgotten member of the human microbiome. This study helps to highlight the complexity of the gut microbiota and the effects its various components (bacteria, viruses, fungi) have on host immunity. These exciting results also provide evidence that supports the epidemiological link between infections and CeD development.