Intestinal epithelial and immune cell responses to Vibrio cholerae and IL22 therapy at single-cell resolution

Knowledge of intestinal cell responses and innate immune defenses to infection with the cholera pathogen is limited. We defined the epithelial and lamina propria immune cell transcriptional responses to experimental cholera using single-cell RNA sequencing using the infant mouse model of V. cholerae infection.

Infection increased the abundance of an enterocyte subtype that highly expressed defense-associated functions, as well as the production of Il22 from ILC3 cells. An IL22 Fc-fusion protein markedly limited V. cholerae intestinal colonization and protected mice from diarrhea and death. IL22 treatment induced expression of vibriocidal Reg3b and elevated the abundance of secretory lineage cells that produce Muc2, impairing V. cholerae association with epithelial cells.