Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells

Author:

Park Eugene1ORCID,Patel Swapneel1,Wang Qiuling2,Andhey Prabhakar3,Zaitsev Konstantin34,Porter Sophia3,Hershey Maxwell1,Bern Michael1,Plougastel-Douglas Beatrice1,Collins Patrick3,Colonna Marco3ORCID,Murphy Kenneth M3,Oltz Eugene35,Artyomov Maxim3,Sibley L David2,Yokoyama Wayne M1ORCID

Affiliation:

1. Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, United States

2. Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, United States

3. Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, United States

4. Computer Technologies Department, ITMO University, Saint Petersburg, Russia

5. Department of Microbial Infection and Immunity, Ohio State University Wexner School of Medicine, Columbus, 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.

Funder

National Institute of Diabetes and Digestive and Kidney Diseases

National Institute of Allergy and Infectious Diseases

National Cancer Institute

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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