MCMV-experienced ILC1 acquire an m12-dependent memory response

Innate and adaptive immune cells can acquire “memory” of encounters with a diverserange of activating signals to tune their response to secondary stimuli. Group 1 innatelymphoid cells (ILC1) are recently discovered tissue-resident sentinels that are essentialfor early host protection from intracellular pathogens at initial sites of infection.However, whether ILC1 function as short-lived effectors or persist and refine theirresponsiveness following pathogen challenge is not well understood. Furthermore,whether pathogen-derived antigens directly modulate tissue-resident ILC responsesremains unclear. Here, we found that liver-resident ILC1 expand locally and persistfollowing the resolution of mouse cytomegalovirus (MCMV) infection. MCMVexperienced ILC1 acquired stable transcriptional, epigenetic, and phenotypic changes,with an enhanced protective effector response to secondary MCMV challenge. Protectivememory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, butnot formed during bystander cytokine activation following heterologous infection. Thus,liver ILC1 acquire adaptive features in a MCMV-specific manner.