Abstract

Innate lymphoid cells (ILCs) were originally classified based on their cytokine profiles, placing natural killer (NK) cells and ILC1s together, but recent studies support their separation into different lineages at steady-state. However, tumors may induce NK cell conversion into ILC1-like cells that are limited to the tumor microenvironment and whether this conversion occurs beyond this environment remains unknown. Here we describe Toxoplasma gondii infection converts NK cells into ILC1-like cells that are distinct from both steady-state NK cells and ILC1s in uninfected mice. These cells were Eomes-dependent, indicating that NK cells can give rise to Eomes- Tbet-dependent ILC1-like cells that circulate widely and persist independent of ongoing infection. Moreover, these changes appear permanent, as supported by epigenetic analyses. Thus, these studies markedly expand current concepts of NK cells, ILCs, and their potential conversion.

Data availability

GEO accession numbers are noted in Materials and Methods. Accession numbers: GSE124313 (RNA-seq, ATAC-seq) and GSE124577 (scRNA-seq).

The following data sets were generated

Article and author information

Author details

  1. Eugene Park

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2617-7571
  2. Swapneel Patel

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Qiuling Wang

    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Prabhakar Andhey

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Konstantin Zaitsev

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Sophia Porter

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Maxwell Hershey

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Michael Bern

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Beatrice Plougastel-Douglas

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Patrick Collins

    Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Marco Colonna

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5222-4987
  12. Kenneth M Murphy

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Eugene Oltz

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Maxim Artyomov

    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. L David Sibley

    Department of Molecular Microbiology, Washington University School of Medicine, St Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Wayne M Yokoyama

    Department of Medicine, Washington University School of Medicine, St Louis, United States
    For correspondence
    yokoyama@wustl.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0566-7264

Funding

National Institute of Diabetes and Digestive and Kidney Diseases (F30DK108472)

  • Eugene Park

National Institute of Allergy and Infectious Diseases (AI128845)

  • Wayne M Yokoyama

National Institute of Allergy and Infectious Diseases (AI120606)

  • Eugene Oltz

National Institute of Allergy and Infectious Diseases (AI134035)

  • Eugene Oltz

National Institute of Allergy and Infectious Diseases (AI134035)

  • Marco Colonna

National Institute of Allergy and Infectious Diseases (AI11852)

  • Eugene Oltz

National Cancer Institute (CA188286)

  • Eugene Oltz

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All protocols were approved by the Institutional Animal Care and Uses Committee(Washington University School of Medicine, St. Louis, MO) under animal protocol number 20160002.

Reviewing Editor

  1. Alan Sher, NIH, NIAID, United States

Publication history

  1. Received: April 11, 2019
  2. Accepted: August 8, 2019
  3. Accepted Manuscript published: August 8, 2019 (version 1)
  4. Version of Record published: August 21, 2019 (version 2)

Copyright

© 2019, Park et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Eugene Park
  2. Swapneel Patel
  3. Qiuling Wang
  4. Prabhakar Andhey
  5. Konstantin Zaitsev
  6. Sophia Porter
  7. Maxwell Hershey
  8. Michael Bern
  9. Beatrice Plougastel-Douglas
  10. Patrick Collins
  11. Marco Colonna
  12. Kenneth M Murphy
  13. Eugene Oltz
  14. Maxim Artyomov
  15. L David Sibley
  16. Wayne M Yokoyama
(2019)
Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells
eLife 8:e47605.
https://doi.org/10.7554/eLife.47605

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