The mammalian innate immune system detects microbial infection through germ line-encoded pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs), and nucleotide-binding oligomerization domain-like receptors (NLRs). These PRRs recognize different but overlapping microbial components and are expressed in various cellular compartments, activating specific signaling pathways that lead to the expression of genes tailored to particular microbes. TLRs, RLRs, and NLRs are crucial for pathogen sensing and innate immune responses. TLRs recognize extracellular pathogens, while RLRs and NLRs detect intracellular pathogens. TLRs are type I transmembrane proteins with LRR domains that mediate recognition of PAMPs. TLRs are divided into cell-surface and intracellular subpopulations, with TLR3, TLR7, TLR8, and TLR9 expressed in intracellular compartments. TLR3 recognizes dsRNA, TLR7 and TLR9 recognize viral nucleic acids, and TLR4 recognizes bacterial LPS. TLRs activate signaling pathways that lead to the production of inflammatory cytokines and type I IFN. RLRs, such as RIG-I and MDA5, detect viral RNA, while NLRs, such as NOD1 and NOD2, recognize bacterial cell wall components. These PRRs also recognize endogenous molecules released during infection or tissue damage, contributing to autoimmune and inflammatory diseases. The signaling pathways of TLRs, RLRs, and NLRs converge on NF-κB and MAPK, which regulate the expression of immune and inflammatory genes. The NALP3 inflammasome is activated by various PAMPs and leads to the release of IL-1β. The NALP1 inflammasome is involved in the recognition of Bacillus anthrax toxin, while the IPAF inflammasome recognizes flagellin. These inflammasomes play critical roles in host defense and immune responses. The signaling pathways of TLRs, RLRs, and NLRs are complex and involve various adapters and kinases, including MyD88, TIRAP, TRIF, TRAF6, and TRAF3, which regulate the activation of NF-κB and MAPK. The activation of these pathways is essential for the innate immune response to pathogens and the regulation of inflammatory and autoimmune diseases.The mammalian innate immune system detects microbial infection through germ line-encoded pattern recognition receptors (PRRs), including Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs), and nucleotide-binding oligomerization domain-like receptors (NLRs). These PRRs recognize different but overlapping microbial components and are expressed in various cellular compartments, activating specific signaling pathways that lead to the expression of genes tailored to particular microbes. TLRs, RLRs, and NLRs are crucial for pathogen sensing and innate immune responses. TLRs recognize extracellular pathogens, while RLRs and NLRs detect intracellular pathogens. TLRs are type I transmembrane proteins with LRR domains that mediate recognition of PAMPs. TLRs are divided into cell-surface and intracellular subpopulations, with TLR3, TLR7, TLR8, and TLR9 expressed in intracellular compartments. TLR3 recognizes dsRNA, TLR7 and TLR9 recognize viral nucleic acids, and TLR4 recognizes bacterial LPS. TLRs activate signaling pathways that lead to the production of inflammatory cytokines and type I IFN. RLRs, such as RIG-I and MDA5, detect viral RNA, while NLRs, such as NOD1 and NOD2, recognize bacterial cell wall components. These PRRs also recognize endogenous molecules released during infection or tissue damage, contributing to autoimmune and inflammatory diseases. The signaling pathways of TLRs, RLRs, and NLRs converge on NF-κB and MAPK, which regulate the expression of immune and inflammatory genes. The NALP3 inflammasome is activated by various PAMPs and leads to the release of IL-1β. The NALP1 inflammasome is involved in the recognition of Bacillus anthrax toxin, while the IPAF inflammasome recognizes flagellin. These inflammasomes play critical roles in host defense and immune responses. The signaling pathways of TLRs, RLRs, and NLRs are complex and involve various adapters and kinases, including MyD88, TIRAP, TRIF, TRAF6, and TRAF3, which regulate the activation of NF-κB and MAPK. The activation of these pathways is essential for the innate immune response to pathogens and the regulation of inflammatory and autoimmune diseases.