Abstract
A high density of microbes inhabits the intestine, helping with food digestion, vitamin synthesis, xenobiotic detoxification, pathogen resistance and immune system maturation. Crucial for human health, communities of commensal bacteria (collectively termed microbiota) benefit in return from a nutrient-rich environment. Host-microbiota mutualism results from a long-term co-adaptation. At barrier surfaces, immune cells distinguish harmful from commensal bacteria and tolerate non-self organisms at close proximity to the mucosa; gut inhabitants have developed strategies to ensure beneficial conditions in their preferred niche. So far, the complex dialogue of host-microbial mutualism is poorly understood. Helicobacter hepaticus is a member of the mouse microbiota that colonizes the lower intestine without inducing immune pathology. However, when there is a host maladaptation such as the absence of the anti-inflammatory cytokine interleukin 10 (IL-10) or its receptor IL-10R, H. hepaticus triggers aberrant IL-23-driven intestinal inflammation. This response results in major changes in the intestinal innate cell compartment, with the accumulation of inflammatory macrophages. Relying both on a bacterial trigger and on an immune defect, H. hepaticus-induced colitis in the context of IL-10/IL-10R axis deficiency shares many features of human inflammatory bowel diseases (IBD). In our study [Danne et al, Cell Host Microbe 22(6):733-745], we questioned the interactions between H. hepaticus and intestinal macrophages that promote mutualism. Our results show that H. hepaticus produces a large polysaccharide that triggers IL-10 production without a corresponding inflammatory response in macrophages. Moreover, H. hepaticus polysaccharide specifically induces an anti-inflammatory gene signature in vitro and in vivo, including transcriptional factors known as repressors of immune activation. This anti-inflammatory program depends on the TLR2/MSK/CREB pathway, which might be crucial to maintain mutualistic relationships at the intestinal interface.