INFLAMMASOMES BRIDGE SIGNALING BETWEEN PATHOGEN IDENTIFICATION AND THE IMMUNE RESPONSE
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)-1β and IL-18. A PAMP such as
lipopolysaccharide can induce production of intracellular pro-IL-1β 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-1β 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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