RESEARCH HIGHLIGHTS Nature Reviews Gastroenterology & Hepatology | Published online 3 May 2017; doi:10.1038/nrgastro.2017.60 COELIAC DISEASE A viral trigger of food insensitivity and coeliac disease? A new study published in Science and also perturbs intestinal immune “We provide evidence that provides evidence that reovirus homeostasis, whereas T3D cannot reovirus can trigger loss of oral T1L … infection infection can disrupt intestinal infect the intestine. By engineering a tolerance and invoke inflammatory promoted a immunohomeostasis and instigate a T3D reassortant virus (T3D-RV) that immune responses to gluten,” harmful immune reaction to dietary can infect the gut, the investigators explains author Bana Jabri. “A virus pro‑inflammatory antigens (such as gluten) in mouse established infection models with that is apparently innocuous … can phenotype … models. The findings point to a two reoviruses with potentially alter in the background, in absence of in response possible role for reovirus infection different immunopathological effects. overt disease, the way the intestinal to dietary as a trigger contributing to the Both T1L and T3D-RV infected immune system sees a dietary development of coeliac disease. the intestine, replicated, induced antigen,” she adds. antigens… Previous epidemiological evidence type 1 T helper (TH1) immune “The most significant finding … is has indicated a role for environmental responses in Peyer’s patches and were the elucidation of a mechanism for factors in the pathogenesis of coeliac ultimately cleared without causing how a virus can shape the immune disease, with studies showing an intestinal damage. response to oral antigens to become association with viruses from the T1L, but not T3D-RV, infection harmful,” notes Ludvig Sollid, Reoviridae family and initiation of promoted a pro-inflammatory University of Oslo, who was not disease. However, experimental data phenotype in mesenteric lymph node involved in the research. “It has been supporting this link were lacking. dendritic cells (DCs) in response suspected that environmental factors The researchers first established to dietary antigens (ovalbumin, other than gluten, in particular a viral infection model in mice using a model antigen). Crucially, the infectious agents, can affect the risk genetically engineered Orthoreovirus tolerogenic phenotype was altered: of contracting coeliac disease; this strains (herein, named reovirus), differentiation of CD4+ T cells into paper presents in an elegant way which are double-stranded RNA peripheral regulatory T (Treg) cells a mechanism for how this can be”. viruses. Two human reovirus was blocked and a TH1 immune However, Sollid emphasizes that isolates — type 1 Lang (T1L) and response to dietary antigens was more work is needed to verify type 3 Dearing (T3D) — that differed promoted instead. This process was that the findings observed in mice in terms of replication biology, dependent on interferon regulatory can be translated to a clinical cellular tropism, pathogenesis, innate factor 1 (IRF1). scenario and that reovirus is truly immune response activation and Crucially, T1L infection induced involved in the aetiology of coeliac intestinal effects were examined; the same switch to TH1 immunity disease in humans. T1L is capable of intestinal infection in response to gluten in transgenic The researchers plan further mice expressing HLA-DQ8 (a key work to define the specific host–viral determinant of coeliac disease). interactions required for virus- Transglutaminase 2 activation, which induced loss of oral tolerance. They has been linked to coeliac disease also hope to investigate whether pathogenesis, was also observed after other viruses could have similar T1L infection. Moreover, patients with immunopathological properties. coeliac disease tended to have higher Katrina Ray anti-reovirus antibody titres (P = 0.06) than those without the condition. ORIGINAL ARTICLE Bouziat, R. et al. Reovirus Indeed, a subset of patients with infection triggers inflammatory responses to d dietary antigens. Science 356, 44–50 (2017) L te coeliac disease on a gluten-free diet au i FURTHER READING Verdu, E. F. et al. Novel ra im M s L with high anti-reovirus antibody titres players in coeliac disease pathogenesis: role of the ar er sha lish ll/Macmillan Pub had markedly increased IRF1 levels in gut microbiota. Nat. Rev. Gastroenterol. Hepatol. 12, 497–506 (2015) small intestinal biopsy samples. NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY www.nature.com/nrgastro ©2017 Mac millan Publishers Li mited, part of Spri nger Nature. All ri ghts reserved. .