Microbial organisms express pathogen-associated molecular patterns (PAMPs) that can stimulate expression of proinflammatory mediators following ligation of pathogen recognition receptors. However, both commensal organisms and pathogens can express PAMPs. The immune system can distinguish between commensals and pathogens in part through secretion of the key inflammatory cytokines interleukin (IL)-1beta and IL-18. A PAMP such as lipopolysaccharide can induce production of intracellular pro-IL-1beta and pro-IL-18, but not their secretion. A second "danger signal", derived from host-cell molecules that are released from stressed or infected cells, or detected as a PAMP that is present in the cytosol, can stimulate assembly of an inflammasome that activates the protease caspase-1. Caspase-1, in turn, is responsible for processing and secretion of the mature IL-1beta and IL-18. Many diverse ligands leading to inflammasome activation have been identified, but the cell signaling pathways initiated by the ligands tend to converge on a small set of common mechanisms.
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