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

Eugene Park,Prabhakar Andhey,Michael Bern,Kenneth M Murphy,Marco Colonna,Maxim Artyomov,Qiuling Wang,Maxwell Hershey,Beatrice Plougastel-Douglas,L David Sibley,Wayne M Yokoyama,Eugene Oltz,Konstantin Zaitsev,Patrick Collins,Sophia Porter,Swapneel Patel

doi:10.7554/elife.47605

Eugene Park, Prabhakar Andhey + Show 14 more

Open Access

https://doi.org/10.7554/elife.47605

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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.

Highlights

Innate lymphoid cells (ILCs) comprise diverse populations
Since anti-NK1.1 affects both natural killer (NK) cells and ILC1s and both have been previously implicated in the immune response to T. gondii (Goldszmid et al, 2012; Klose et al, 2014), we sought to investigate how NK cells and ILC1s respond to infection
There was a small population of spleen cells resembling ILC1s in uninfected mice, even though ILC1s are primarily found in other organs including the liver and small intestine and are generally tissue-resident (Sojka et al, 2014a; Fuchs et al, 2013), whereas cells in the spleen are generally circulating cells (Gasteiger et al, 2015; Sojka et al, 2014a; Peng et al, 2013)

Summary

Introduction

Innate lymphoid cells (ILCs) comprise diverse populations. Like T and B cells, they are derived from common lymphoid progenitors (CLPs) but do not undergo antigen receptor recombination (Spits and Cupedo, 2012). Whereas ILC1s are restricted to organs, and CD49a expression is a faithful marker of tissue-resident populations under steady-state conditions (Peng et al, 2013; Sojka et al, 2014a), most NK cells freely circulate. ILC1s are completely Tbet-dependent (Daussy et al, 2014; Sojka et al, 2014a), whereas NK cells require Tbet only for maturation (Townsend et al, 2004; Gordon et al, 2012). Independent examination of each population, especially in settings known to stimulate NK cells and ILC1s, is required to better understand these cells and their relationship to each other. We found that ILC1s become permanently heterogeneous after infection, largely owing to the surprising conversion of NK cells into ILC1-like cells

Results

Discussion

Materials and methods