Quiescent ILC1 cells confer protection against MCMV infection during undernutrition

In the liver, group 1 innate lymphoid cells (ILCs) comprise 10%-20% tissue-resident ILC1 cells and 80%-90% conventional natural killer (NK) cells. Both cell types contribute to early defense against virus infection by secreting interferon γ (IFN-γ). However, the distinct role of ILC1 cells in viral infection remains incompletely understood. Here, we identify that ILC1 cells outnumber NK cells, constituting 80%-90% of group 1 ILCs in the liver during undernutrition. Mechanistically, undernutrition significantly reduces NK cell numbers, while hepatic ILC1 cells enter a quiescent state that allows them to survive in an mTORC1-dependent manner. Metabolically, quiescent ILC1 cells exhibit greater glucose uptake than NK cells and efficiently utilize it via oxidative phosphorylation, which is induced by mTORC1. Finally, ILC1-deficient mice succumb to murine cytomegalovirus (MCMV) infection under undernourished conditions but not when fed ad libitum. These findings suggest a non-redundant function of hepatic ILC1 cells in protecting the host against MCMV infection during undernutrition.