Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells
Hong Yu, Hyungjun Yang, Joannie M. Allaire, Caixia Ma, Franziska A. Graef, Arthur Mortha, Qiaochu Liang, Else S. Bosman, Gregor S. D. Reid, James A. Waschek, Lisa C. Osborne, Harry Sokol, Bruce A. Vallance, Kevan Jacobson
Abstract
Significance Group 3 innate lymphoid cells enriched in the gut mediate host resistance against intestinal pathogens. Their function and development can be regulated by diverse factors, including neuropeptides secreted by the enteric nervous system. We show that the neuropeptide vasoactive intestinal peptide (VIP) promotes the recruitment of these innate lymphoid cells and other immune cells to the gut through a receptor. Mice lacking VIP or its receptor were highly susceptible to an enteric pathogen infection. Replenishing the innate lymphoid cells or their secreted products into these mice was able to partially or fully restore host resistance to the infection. Thus, the enteric nervous system, through VIP, regulates the recruitment of innate lymphoid cells to the gut, offering protection against enteric pathogens.