Innate immune recognition of intracellular pathogens and danger signals is mediated by pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-like helicases (RLHs). TLRs detect extracellular pathogens, while NLRs and RLHs sense intracellular invaders. NLRs, such as NOD2 and NALP3, recognize bacterial peptidoglycan and other danger signals, triggering inflammatory responses through the activation of caspase-1 and the processing of pro-inflammatory cytokines like IL-1β. NOD2 mutations are linked to inflammatory diseases such as Crohn's disease, while NALP3 is involved in autoinflammatory disorders. The NALP3 inflammasome is activated by bacterial components and host-derived danger signals, including uric acid crystals and potassium efflux. RLHs, such as RIG-I and MDA5, detect viral RNA and initiate antiviral responses through the production of type I interferons. These receptors play critical roles in host defense, but their dysregulation can lead to chronic inflammation and autoimmune diseases. Understanding their mechanisms is essential for developing targeted therapies for inflammatory and autoimmune conditions.Innate immune recognition of intracellular pathogens and danger signals is mediated by pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), NOD-like receptors (NLRs), and RIG-like helicases (RLHs). TLRs detect extracellular pathogens, while NLRs and RLHs sense intracellular invaders. NLRs, such as NOD2 and NALP3, recognize bacterial peptidoglycan and other danger signals, triggering inflammatory responses through the activation of caspase-1 and the processing of pro-inflammatory cytokines like IL-1β. NOD2 mutations are linked to inflammatory diseases such as Crohn's disease, while NALP3 is involved in autoinflammatory disorders. The NALP3 inflammasome is activated by bacterial components and host-derived danger signals, including uric acid crystals and potassium efflux. RLHs, such as RIG-I and MDA5, detect viral RNA and initiate antiviral responses through the production of type I interferons. These receptors play critical roles in host defense, but their dysregulation can lead to chronic inflammation and autoimmune diseases. Understanding their mechanisms is essential for developing targeted therapies for inflammatory and autoimmune conditions.