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.
GEO accession numbers are noted in Materials and Methods. Accession numbers: GSE124313 (RNA-seq, ATAC-seq) and GSE124577 (scRNA-seq).
Gene transcription and chromatin accessibility of conventional NK cells and ILC1s in spleens of uninfected and Toxoplasma gondii-infected MiceNCBI Gene Expression Omnibus, GSE124313.
Toxoplasma gondii Infection Promotes NK Cell Conversion into ILC1s and Heterogeneous ILC1 PopulationsNCBI Gene Expression Omnibus, GSE124577.
- Eugene Park
- Wayne M Yokoyama
- Eugene Oltz
- Eugene Oltz
- Marco Colonna
- Eugene Oltz
- Eugene Oltz
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
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.
- Alan Sher, NIH, NIAID, United States
© 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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