Type I Innate Lymphoid Cells Sense and Proliferate in Response to Distal Viral Infection

Abstract Innate lymphoid cells (ILCs) are a diverse group of tissue-resident lymphocytes that lack antigen-specific receptors commonly found on adaptive immune cells. While many different types of ILCs have been described, only group 1 ILCs (ILC1s) are known to exhibit marked antiviral activity. We recently described ILC1-mediated protection of the oral mucosa, a critical barrier tissue and site of continued pathogen exposure. Based on these studies, we hypothesized that these innate antiviral cells might also respond to inflammation induced by a distal viral infection. To address this, we used a common mouse model of vaccinia virus (VACV) infection of the peritoneal cavity, which spreads locally but does not result in infection of the oral mucosa. Confocal microscopy of frozen sections of the lip demonstrated a marked increase in the number and density of oral mucosal ILC1s in response to distal infection. Further, ILC1s remained sustainably elevated for weeks following the initial infection. Ongoing experiments will assess the ability of this enhanced layer of ILC1s to provide heightened antiviral immunity in the oral mucosa and determine the timeframes in which this occurs. Together, our data suggest that the ability of ILC1s to globally sense infection and enhance protection in response to distal infection may represent a previously unappreciated mechanism of trained immunity in the tissue.