Single-cell resolution of the adult zebrafish intestine under conventional conditions and in response to an acute Vibrio cholerae infection

• Published in: Cell reports (Cambridge) 2023-11, Vol.42 (11), p.113407-113407, Article 113407
• Main Authors: Jones, Lena O., Willms, Reegan J., Xu, Xinyue, Graham, Ralph Derrick V., Eklund, Mckenna, Shin, Minjeong, Foley, Edan
• Format: Article
• Language: English
• Subjects: Animals; Cholera - microbiology; CP: Immunology; CP: Microbiology; interferon; Interferons; Intestines - microbiology; intraepithelial leukocytes; Mammals; single-cell RNA sequencing; Vibrio cholerae; Zebrafish - microbiology; Zebrafish intestine
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2023.113407

Vibrio cholerae is an aquatic bacterium that causes severe and potentially deadly diarrheal disease. Despite the impact on global health, our understanding of host mucosal responses to Vibrio remains limited, highlighting a knowledge gap critical for the development of effective prevention and treatment strategies. Using a natural infection model, we combine physiological and single-cell transcriptomic studies to characterize conventionally reared adult zebrafish guts and guts challenged with Vibrio. We demonstrate that Vibrio causes a mild mucosal immune response characterized by T cell activation and enhanced antigen capture; Vibrio suppresses host interferon signaling; and ectopic activation of interferon alters the course of infection. We show that the adult zebrafish gut shares similarities with mammalian counterparts, including the presence of Best4+ cells, tuft cells, and a population of basal cycling cells. These findings provide important insights into host-pathogen interactions and emphasize the utility of zebrafish as a natural model of Vibrio infection. [Display omitted] •The adult zebrafish intestine houses a complex community of specialist epithelial cells•The adult zebrafish intestine associates with sub- and intraepithelial leukocytes•V. cholerae suppresses the interferon pathway throughout the zebrafish intestine during an infection Jones et al. use single-cell RNA sequencing to profile the adult zebrafish intestine under homeostatic conditions and in response to infection by Vibrio cholerae, the causative agent of cholera. They identify a diversity of intestinal cell types and show how each cell responds to Vibrio cholerae.