Fig. 1.
Pattern recognition receptors in immunity and their involvement in sterile and sepsis-related inflammation. Pattern recognition receptors (PRRs) expressed by antigen presenting cells (dendritic cells, monocytes, macrophages) constitute the first interaction between the extra-cellular environment and innate immunity. They are proteins, which include membrane-bound and cytoplasmic receptors that bind either pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) derived from exogenous microorganisms (i.e., sepsis from infection) or endogenous molecules (i.e., sterile inflammation). Interaction of PRRs with PAMPs/DAMPs induces nuclear factor-kappa B signaling pathways, resulting in the secretion of proinflammatory cytokines and co-stimulatory molecules. In sepsis, the initial immune response triggered by PAMPs/PRRs interaction can lead to tissue damage and the release of DAMPs, which may act synergistically with PAMPs to enhance inflammation. Nevertheless, even without microorganism involvement, DAMPs released from dead or dying cells in response to injury or stress, are able to induce similar proinflammatory cytokine production from tissues, driving “sterile inflammation.” ATP = adenosine triphosphate; DAMPs = damage-associated molecular patterns; IL-1β = interleukin-1 beta; IL-6 = interleukin 6; IL-18 = interleukin 18; LPS = lipopolysaccharide; M-CSF = macrophage colony-stimulating factor; NF-κB = nuclear factor kappa-light-chain-enhancer of activated B cells; PAMPs = pathogen-associated molecular patterns; PRRs = pattern recognition receptors; S100A8/9 = (also known as calgranulins A and B, or MRP8 and MRP14, respectively) members of the S100 multigene subfamily of cytoplasmic EF-hand Ca2+-binding proteins which are endogenous activators of Toll-like receptor 4; TNF = tumor necrosis factor.