Unveiling the sensing potential of innate lymphoid cells

Innate lymphoid cells (ILCs) are key regulators of early immune responses and play a central role in mucosal immunity, where they contribute to host defense and tissue homoeostasis. This review synthesizes evidence that ILCs, including natural killer cells (NKs), ILC1s, ILC2s, ILC3s, and lymphoid tissue inducer (LTi) cells, directly sense pathogens via pattern recognition receptors (PRRs). Beyond their established role as cytokine responders, emerging data reveal that ILCs engage PRRs to initiate complementary, context-dependent signaling pathways. This direct recognition mechanism redefines the functional landscape of ILCs in early immune surveillance, moving beyond reliance on indirect stromal signals. Collectively, these insights reposition ILCs as active sentinels in host defense and highlight the ILC-PRR axis as a novel therapeutic avenue for modulating immune responses in infectious, inflammatory, and cancer-related diseases. This review summarizes how innate lymphoid cell—beyond cytokine responder roles—directly sense pathogens via pattern recognition receptors, reshaping innate immunity and informing new antiviral and cancer immunotherapy strategies.