Abstract
SummaryInteractions between the host and its microbiota are of mutual benefit and promote health. Complex molecular pathways underlie this dialog, but the identity of microbe-derived molecules that mediate the mutualistic state remains elusive. Helicobacter hepaticus is a member of the mouse intestinal microbiota that is tolerated by the host. In the absence of an intact IL-10 signaling, H. hepaticus induces an IL-23-driven inflammatory response in the intestine. Here we investigate the interactions between H. hepaticus and host immune cells that may promote mutualism, and the microbe-derived molecule(s) involved. Our results show that H. hepaticus triggers early IL-10 induction in intestinal macrophages and produces a large soluble polysaccharide that activates a specific MSK/CREB-dependent anti-inflammatory and repair gene signature via the receptor TLR2. These data identify a host-bacterial interaction that promotes mutualistic mechanisms at the intestinal interface. Further understanding of this pathway may provide novel prevention and treatment strategies for inflammatory bowel disease.
Highlights
Shaped by a long history of co-evolution, the relationship between mammalian hosts and their intestinal commensal bacteria is of mutual benefit and promotes health
Our results show that H. hepaticus induces an early IL-10 response by intestinal macrophages and produces a large soluble polysaccharide that activates a specific mitogen and stress-activated protein kinase (MSK)/ cAMP response element-binding protein (CREB)-dependent anti-inflammatory and repair gene signature via the receptor TLR2
H. hepaticus Induces IL-10 in Gut-Resident Macrophages As blockade of IL-10 signaling induces colitis in mice colonized with H. hepaticus (Kullberg et al, 2006; Morrison et al, 2013), we first assessed whether H. hepaticus interacts directly with the innate immune compartment within the intestinal mucosa to trigger IL-10 production
Summary
Shaped by a long history of co-evolution, the relationship between mammalian hosts and their intestinal commensal bacteria is of mutual benefit and promotes health. Appropriate host immune regulatory responses are crucial, as H. hepaticus infection of lymphocyte-replete mice with geneticor pharmacological-induced deficiencies of the interleukin-10/ interleukin-10 receptor (IL-10/IL-10R) pathway results in colitis and typhlitis (Kullberg et al, 1998, 2006; Morrison et al, 2013) Under these circumstances, there is an aberrant IL-23driven inflammatory response in the intestine with accumulation of pro-inflammatory granulocytes and monocytes that contributes to disease pathology (Arnold et al, 2016; Griseri et al, 2012; Hue et al, 2006; Krausgruber et al, 2016). Little is known about the interaction of H. hepaticus with the innate immune compartment and its capacity to induce IL-10 production by these cells
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