Antiviral Activities of Group I Innate Lymphoid Cells

Even before the adaptive immune response initiates, a potent group of innate antiviral cells responds to a wide range of viruses to limit replication and virus-induced pathology. Belonging to a broader family of recently discovered innate lymphoid cells (ILCs), antiviral group I ILCs are composed of conventional natural killer cells (cNK) and tissue-resident ILCs (ILC1s) that can be distinguished based on their location as well as by the expression of key cell surface markers and transcription factors. Functionally, blood-borne cNK cells recirculate throughout the body and are recruited into the tissue at sites of viral infection where they can recognize and lyse virus-infected cells. In contrast, ILC1s are poised in uninfected barrier tissues and respond not through lysis but with the production of antiviral cytokines. From their frontline tissue locations, ILC1s can even induce an antiviral state in uninfected tissue to preempt viral replication. Mounting evidence also suggests that ILC1s may have enhanced secondary responses to viral infection. In this review, we discuss recent findings demonstrating that ILC1s provide several critical layers of innate antiviral immunity and the mechanisms (when known) underlying protection.