MCMV-experienced ILC1 acquire an m12-dependent memory response

Innate and adaptive immune cells can acquire “memory” of encounters with a diverse range of activating signals to tune their response to secondary stimuli. Group 1 innate lymphoid cells (ILC1) are recently discovered tissue-resident sentinels that are essential for early host protection from intracellular pathogens at initial sites of infection. However, whether ILC1 function as short-lived effectors or persist and refine their responsiveness following pathogen challenge is not well understood. Furthermore, whether pathogen-derived antigens directly modulate tissue-resident ILC responses remains unclear. Here, we found that liver-resident ILC1 expand locally and persist following 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. Protective memory ILC1 responses were dependent on the MCMV-encoded glycoprotein m12, but not formed during bystander cytokine activation following heterologous infection. Thus, liver ILC1 acquire adaptive features in a MCMV-specific manner. RNA and ATAC sequencing analysis of sorted liver ILC1 from naïve and MCMV experienced WT mice. PRJNA528997 SRP189404