Respiratory Influenza Virus Infection Causes Dynamic Tuft Cell and Innate Lymphoid Cell Changes in the Small Intestine

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Abstract

Influenza A viruses (IAV) can cause severe disease and death in humans. IAV infection and the accompanying immune response can result in systemic inflammation, leading to intestinal damage and disruption of the intestinal microbiome. Here, we demonstrate that a specific subset of epithelial cells, tuft cells, increase across the small intestine during active respiratory IAV infection. Upon viral clearance, tuft cell numbers return to baseline levels. Intestinal tuft cell increases were not protective against disease, as animals with either increased tuft cells or a lack of tuft cells did not have any change in disease morbidity after infection. Respiratory IAV infection also caused transient increases in type 1 and 2 innate lymphoid cells (ILC1 and ILC2, respectively) in the small intestine. ILC2 increases were significantly blunted in the absence of tuft cells, whereas ILC1s were unaffected. Unlike the intestines, ILCs in the lungs were not altered in the absence of tuft cells. This work establishes that respiratory IAV infection causes dynamic changes to tuft cells and ILCs in the small intestines and that tuft cells are necessary for the infection-induced increase in small intestine ILC2s. These intestinal changes in tuft cell and ILC populations may represent unexplored mechanisms preventing systemic infection and/or contributing to severe disease in humans with preexisting conditions. IMPORTANCE Influenza A virus (IAV) is a respiratory infection in humans that can lead to a wide range of symptoms and disease severity. Respiratory infection can cause systemic inflammation and damage in the intestines. Few studies have explored how inflammation alters the intestinal environment. We found that active infection caused an increase in the epithelial population called tuft cells as well as type 1 and 2 innate lymphoid cells (ILCs) in the small intestine. In the absence of tuft cells, this increase in type 2 ILCs was seriously blunted, whereas type 1 ILCs still increased. These findings indicate that tuft cells are necessary for infection-induced changes in small intestine type 2 ILCs and implicate tuft cells as regulators of the intestinal environment in response to systemic inflammation.

Original languageEnglish (US)
JournalJournal of virology
Volume96
Issue number9
DOIs
StatePublished - May 2022

Bibliographical note

Funding Information:
S.N.R., J.K.F., and F.K.S. were supported by National Institutes of Health T32 HL007741. Diagrams were created with BioRender.

Funding Information:
We thank the University of Minnesota Flow Cytometry Resource Facility and University Imaging Center, especially Jason Mitchell, for technical support of these studies. We also thank the DNA Services team at the University of Illinois at Urbana-Champaign Roy J. Carver Biotechnology Center for technical support of the 16S sequencing. We also thank the Masopust and Vezys laboratories, especially Sathi Wijeyesinghe, at the University of Minnesota for assistance with SI protocol development. We also thank the entire Langlois laboratory at the University of Minnesota for continued feedback throughout the duration of these studies. S.N.R., J.K.F., and F.K.S. were supported by National Institutes of Health T32 HL007741. Diagrams were created with BioRender.

Publisher Copyright:
Copyright © 2022 American Society for Microbiology. All Rights Reserved.

Keywords

  • KEYWORDS influenza virus
  • innate lymphoid cells
  • tuft cells

PubMed: MeSH publication types

  • Journal Article

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