TY - JOUR
T1 - Toxoplasma gondii infection drives conversion of NK cells into ILC1-like cells
AU - Park, Eugene
AU - Patel, Swapneel
AU - Wang, Qiuling
AU - Andhey, Prabhakar
AU - Zaitsev, Konstantin
AU - Porter, Sophia
AU - Hershey, Maxwell
AU - Bern, Michael
AU - Plougastel-Douglas, Beatrice
AU - Collins, Patrick
AU - Colonna, Marco
AU - Murphy, Kenneth M.
AU - Oltz, Eugene
AU - Artyomov, Maxim
AU - Sibley, L. David
AU - Yokoyama, Wayne M.
N1 - Funding Information:
We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1 TR000448 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH.
Funding Information:
National Institute of Diabetes and Digestive and Kidney Diseases, F30DK108472, National Institute of Allergy and Infectious DiseasesAI120606, National Institute of Allergy and Infectious Diseases AI134035, National Institute of Allergy and Infectious Diseases AI11852, National Cancer Institute CA188286, National Institute of Allergy and Infectious Diseases AI128845
Funding Information:
This work was supported by NIH grants F30DK108472 (EP), AI128845 (WMY), AI120606 (EMO), AI134035 (EMO, MC), AI11852 (EMO), and CA188286 (EMO). We thank members of the Yokoyama Lab, Ilija Brizic, Stipan Jonjic, and Victor Cortez for helpful discussions, Jennifer Barks and Reeha Savari Dhason for HFF cells, Nathaniel Jones, Sumit Kumar, Josh Radke, and Kevin Brown for T. gon-dii strains, Suzanne Hickerson for technical assistance, and Lacey Feigl, Lorraine Schwartz, and Shirley McTigue for administrative assistance.
Publisher Copyright:
© Park et al.
PY - 2019/8
Y1 - 2019/8
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85071705267&partnerID=8YFLogxK
U2 - 10.7554/eLife.47605
DO - 10.7554/eLife.47605
M3 - Article
C2 - 31393266
AN - SCOPUS:85071705267
SN - 2050-084X
VL - 8
JO - eLife
JF - eLife
M1 - e47605
ER -