In this project, we have been exploring how nervous cells perceive, integrate and respond to commensal microorganisms or their products. Initially, we have explored the presence of the different pattern recognition receptors and their adaptors in the enteric neurons and glial cells. We have found that enteric nervous cells mainly rely on MYD88-mediated sensing in comparison to other sensing mechanisms, interestingly nervous MYD88 expression is comparable to its expression by other immune cells. This was true for in vitro generated neurosphere-derived neurons and glial cells and neurons and glial cells purified from the intestine.
In parallel, we have analyzed the nervous cells-mediated microbial sensing impact on the enteric immune system functionality, particular on the innate lymphoid cells (ILC)-type 2 function. Notably, we found that neuronal-MYD88-sensing of commensal microorganisms or their signals is essential for neuron-derived regulators, particular the cholinergic (Chat+) neurons function. This neuronal sensing promotes the intestinal ILC2 functionality at the level of cytokines production. In contrast, glial cells MYD88-mediated sensing of microbiota suppresses ILC2 activity.
Moreover, this active neuronal and/or glial cells MYD88-sensing of commensal microorganisms impacts on the ENS functionality, particularly the intestinal motility. Our results indicate that the intestinal motility is inhibited by glial cells-mediated microbial sensing whereas is promoted by adrenergic (Th+) neuron-mediated commensals detection and not affected by cholinergic (Chat+) neuron-mediated microbial sensing.
These results will be included in future peer-reviewed articles for their exploitation and dissemination.
