Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization

Aline Ignacio; Kathleen Shah; Jeremiah Bernier-Latmani; Yasmin Köller; Gillian Coakley; Mati Moyat; Romain Hamelin; Florence Armand; Nick C Wong; Hena Ramay; Carolyn A Thomson; Regula Burkhard; Haozhe Wang; Antoine Dufour; Markus B Geuking; Braedon McDonald; Tatiana V Petrova; Nicola L Harris; Kathy D McCoy

doi:10.1016/j.immuni.2022.05.014

Small intestinal resident eosinophils maintain gut homeostasis following microbial colonization

Immunity. 2022 Jul 12;55(7):1250-1267.e12. doi: 10.1016/j.immuni.2022.05.014. Epub 2022 Jun 15.

Authors

Aline Ignacio¹, Kathleen Shah², Jeremiah Bernier-Latmani³, Yasmin Köller⁴, Gillian Coakley⁵, Mati Moyat⁶, Romain Hamelin⁷, Florence Armand⁷, Nick C Wong⁸, Hena Ramay⁹, Carolyn A Thomson¹, Regula Burkhard¹⁰, Haozhe Wang⁵, Antoine Dufour¹¹, Markus B Geuking¹⁰, Braedon McDonald¹², Tatiana V Petrova¹³, Nicola L Harris¹⁴, Kathy D McCoy¹⁵

Affiliations

¹ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
² Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK.
³ Department of Oncology, Ludwig Institute for Cancer Research Lausanne, University of Lausanne (UNIL), Chemin des Boveresses 155, Epalinges, Switzerland.
⁴ Maurice Müller Laboratories, Department of Biomedical Research, Universitätsklinik für Viszerale Chirurgie und Medizin Inselspital, University of Bern, Murtenstrasse 35, 3008 Bern, Switzerland.
⁵ Department of Immunology and Pathology, Central Clinical School, Monash University, The Alfred Centre, Melbourne, VIC, Australia.
⁶ Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; Department of Immunology and Pathology, Central Clinical School, Monash University, The Alfred Centre, Melbourne, VIC, Australia.
⁷ Proteomics Core Facility, Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland.
⁸ Monash Bioinformatics Platform, Monash University, Clayton, VIC 3168, Australia.
⁹ International Microbiome Centre, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹⁰ Department of Microbiology, Immunology and Infectious Diseases, Snyder Institute of Chronic Diseases, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
¹¹ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada; McCaig Institute for Bone and Joint Health, University of Calgary, Calgary, AB T2N 4N1, Canada.
¹² Department of Critical Care Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4A1, Canada.
¹³ Department of Oncology, Ludwig Institute for Cancer Research Lausanne, University of Lausanne (UNIL), Chemin des Boveresses 155, Epalinges, Switzerland; Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology Lausanne, Route Cantonale, 1015 Lausanne, Switzerland.
¹⁴ Global Health Institute, Swiss Federal Institute of Technology, Lausanne, 1015 Lausanne, Switzerland; Department of Immunology and Pathology, Central Clinical School, Monash University, The Alfred Centre, Melbourne, VIC, Australia. Electronic address: nicola.harris@monash.edu.
¹⁵ Department of Physiology and Pharmacology, Snyder Institute for Chronic Diseases, University of Calgary, Cumming School of Medicine, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada. Electronic address: kathy.mccoy@ucalgary.ca.

PMID: 35709757
DOI: 10.1016/j.immuni.2022.05.014

Abstract

The intestine harbors a large population of resident eosinophils, yet the function of intestinal eosinophils has not been explored. Flow cytometry and whole-mount imaging identified eosinophils residing in the lamina propria along the length of the intestine prior to postnatal microbial colonization. Microscopy, transcriptomic analysis, and mass spectrometry of intestinal tissue revealed villus blunting, altered extracellular matrix, decreased epithelial cell turnover, increased gastrointestinal motility, and decreased lipid absorption in eosinophil-deficient mice. Mechanistically, intestinal epithelial cells released IL-33 in a microbiota-dependent manner, which led to eosinophil activation. The colonization of germ-free mice demonstrated that eosinophil activation in response to microbes regulated villous size alterations, macrophage maturation, epithelial barrier integrity, and intestinal transit. Collectively, our findings demonstrate a critical role for eosinophils in facilitating the mutualistic interactions between the host and microbiota and provide a rationale for the functional significance of their early life recruitment in the small intestine.

Keywords: eosinophil; extracellular matrix; germ-free; intestinal barrier; microbiome; small intestine; tissue homeostasis; villous atrophy.

Publication types

Research Support, U.S. Gov't, Non-P.H.S.
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Communicable Diseases*
Eosinophils
Homeostasis
Intestinal Mucosa
Intestine, Small
Mice
Microbiota*

Grants and funding

PJT-165930/CIHR/Canada