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

L.O. Jones; R.J. Willms; X. Xu; R.D.V. Graham; M. Eklund; M. Shin; E. Foley

doi:10.1016/j.celrep.2023.113407

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

L.O. Jones, R.J. Willms, X. Xu, R.D.V. Graham, M. Eklund, M. Shin, E. Foley

University of Alberta

Research output: Contribution to journal › Article › peer-review

12 Citations (SciVal)

Abstract

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.

Original language	English
Article number	113407
Journal	Cell Reports
Volume	42
Issue number	11
Early online date	9 Nov 2023
DOIs	https://doi.org/10.1016/j.celrep.2023.113407
Publication status	Published - 28 Nov 2023

Data Availability Statement

Single-cell RNA-seq raw data files have been deposited to the NCBI GEO database and are publicly available (NCBI GEO
(GSE230044)). Processed single-cell RNA-seq data have been deposited at the Broad Institute Single Cell Portal and are publicly available (https://singlecell.broadinstitute.org/single_cell/study/SCP2141/adult-zebrafish-intestine#study-visualize). GEO
accession number and Portal link are listed in the key resources table.
d This paper does not report original code.
d Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon
request.

Funding

Vibrio cholerae strains used in this project were provided by Dr. Stefan Pukatzki. Imaging experiments were performed at the University of Alberta Faculty of Medicine & Dentistry (FoMD) Cell Imaging Core, RRID: SCR_019200, which receives financial support from FoMD, the Department of Medical Microbiology and Immunology, the University Hospital Foundation, and Canada Foundation for Innovation (CFI) awards to contributing investigators. Transmission electron microscopy experiments were performed at the Department of Oncology Cell Imaging Facility. Flow cytometry experiments were performed at the FoMD Flow Cytometry Facility, RRID: SCR_019195, which receives financial support from FoMD, the Li Ka Shing Institute of Virology, University of Alberta, and CFI awards to contributing investigators. Singlecell libraries were prepared at the FoMD High Content Analysis Core, RRID: SCR_019182, which receives financial support from FoMD, the Li Ka Shing Institute of Virology, and CFI awards to contributing investigators. Immunohistochemistry experiments were performed at the Faculty of Science Department of Biological Sciences Advanced Microscopy Facility. We would also like to thank Science Animal Support Services and the Alberta Health Sciences Animal Laboratory Services for their excellent care of the zebrafish aquatics facilities. This work was supported by grants from the Canadian Institutes of Health Research (grant no. MOP77746) and the Weston Family Microbiome Initiative to E.F. R.J.W. has funding support through the National Science and Engineering Research Council Graduate Scholarships, and Alberta Innovates Graduate Student Scholarships.

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

Abstract

Data Availability Statement

Funding

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