Innate Immune Detection of Bacterial Virulence Factors Via the NLRC4 Inflammasome
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Cytokine production by innate immune cells is initiated by signaling downstream of pattern recognition receptors, including Toll-like receptors.
A subset of cytokines, including IL-1β and IL-18, require post-translational proteolysis before secretion, which provides a second mechanism of regulation. This proteolysis is dependent upon caspase 1, which is activated by Nod-like receptor (NLR) signaling. NLRC4 (previously named Ipaf) activates caspase 1 in response to bacterial virulence factors including type III and IV secretion systems (T3SS and T4SS). NLRC4 recognizes T3SS/T4SS in two ways: indirectly by detecting flagellin, and directly by detecting the T3SS rod protein. Both flagellin and rod protein are unintentionally delivered to the mammalian cytosol by the bacterium through the T3SS.
KeywordsNLRC4 caspase 1 IL-1β type III secretion inflammation