Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells
- Washington University School of Medicine, United States
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).
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Toxoplasma gondii Infection Promotes NK Cell Conversion into ILC1s and Heterogeneous ILC1 PopulationsNCBI Gene Expression Omnibus, GSE124577.
Article and author information
Author details
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
- Alan Sher, NIH, NIAID, United States
Publication history
- Received: April 11, 2019
- Accepted: August 8, 2019
- Accepted Manuscript published: August 8, 2019 (version 1)
- 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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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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