Targeting innate immune sensors for therapeutic strategies in infectious diseases

The innate immune system relies on innate immune sensors, such as pattern recognition receptors (PRRs), to detect pathogens and initiate immune responses, crucial for controlling infections but also implicated in inflammatory diseases. These innate immune sensors, including Toll-like receptors (TLRs), nod-like receptors (NLRs), RIG-I-like receptors (RLRs), absent in melanoma 2 (AIM2), and Z-DNA binding protein 1 (ZBP1) trigger signaling pathways that produce cytokines, modulating inflammation and cell death. Traditional therapies focus on directly targeting pathogens; however, host-targeting therapeutic strategies have emerged as innovative approaches to modulate innate immune sensor activity. These strategies aim to fine-tune the immune response, either enhancing antiviral defenses or mitigating hyperinflammation to prevent tissue damage. This review explores innate immune sensor-based therapeutic approaches, including inhibitors, agonists, and antagonists, that enhance antiviral defense or suppress harmful inflammation, highlighting innate immune sensors as promising targets in infectious and inflammatory disease treatment.