Toxoplasma gondii infection drives conversion of NK Cells into ILC1s

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 cells resembling steady-state ILC1s that are heterogeneous and distinct from both steady-state NK cells and ILC1s in uninfected mice. Most toxoplasma-induced ILC1s 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.