The murine intestinal pathobiont Helicobacter hepaticus attenuates DSS colitis in a CD4+ T cell-dependent manner

The host immune system is fundamentally shaped by its resident microbiota; however, much remains unknown about how individual microbial species contribute to health and disease. Helicobacter hepaticus ( Hh ) is a member of the murine intestinal microbiota associated with colitis in immunodeficient mice, despite driving dominant immune regulatory responses in normal hosts which allow colonization without pathology. However, whether this colonization influences intestinal immune homeostasis more widely remains unexplored. Here, we report that Hh colonization confers a disease protective effect on DSS colitis, attenuating intestinal inflammation and other disease parameters. Disease attenuation required persistent colonization and was dependent on host CD4 ⁺ T cells. We further show that Hh colonization promotes a conserved anti-inflammatory transcriptional programme across several effector and regulatory intestinal CD4 ⁺ T cell subsets. Thus, although persistent stimulation of host immune responses allows the host to tolerate ‘pathobionts’ like Hh , this is compensated by the promotion of tissue-protective immunological conditioning.