Respiratory gammaherpesvirus infection exacerbates experimental model of inflammatory bowel disease

Inflammatory bowel diseases (IBD) is a widespread disease worldwide that affects the quality of life of all age groups. Although the precise etiology is still poorly defined, multiple factors, such as genetic background, environmental triggers, and mucosal immune dysregulation, have been associated to the pathogenesis. Epidemiological studies in humans have proposed a key influence of gammaherpesvirus (γHV) infections given that Epstein Barr virus has been associated with the development and exacerbation of IBD. However, the presence of confounding factors makes it difficult to distinguish between a causal role from an innocent side effect. In this study, we used dextran sulfate sodium (DSS)-induced colitis and Murid herpesvirus 4 (MuHV-4) to investigate in mice whether and how γHV infection could shape deleterious immune responses responsible for IBD exacerbation. By monitoring weight loss, clinical scoring and pathological lesions, we demonstrated a significant exacerbation of experimental colitis in MuHV-4-infected individuals. Interestingly, immunophenotyping of leukocytes isolated from the lamina propria revealed a massive increase in T cell infiltration in the colon of MuHV-4 pre-infected mice. These T cells show major phenotypic changes such as overexpression of activation markers and exacerbation of cytotoxic properties. These differences correlate with an enhanced Th-1 response in draining lymph nodes, consistent with a significant accumulation of CXCL9-producing monocytes that could attract T cells but also dictate their cytotoxic polarization. Overall, these initial data highlight the ability of certain γHV to trigger deleterious intestinal immune responses that could explain some inter-individual differences in IBD susceptibility.