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IPAF and NAIP5
IPAF (NLRC4, CLAN/CARD12) and NAIP5 constitute another set of NLRs.
IPAF belongs to the CARD subfamily whereas NAIP5 is a member of the
BIR subfamily. Both NLRs have been shown to respond to flagellin, the main
component of the bacterial flagellum, restricting the proliferation of
intracellular bacteria such as Salmonella typhimurium, Shigella flexneri and
Legionella pneumophila. IPAF senses flagellin from S. typhimurium and S. flexneri
secreted by the bacterial type III secretion system (TTSS). SipB in S.
typhimurium and IpaB in S. flexneri are part of a TTSS and are required for
Caspase-1 activation. These proteins participate in the translocation of
flagellin in the cytosol by forming a pore in the host-cell membrane.
Caspase-1 activation induced by cytosolic flagellin has been shown to be
IPAF-dependent, but TLR5-independent 19 . Thus TLR5 and IPAF appear to
be two different sensors that respond to extracellular and cytosolic flagellin,
respectively 20 .The adaptor ASC seems to be involved in Caspase-1 activation
in response to infection with S. typhimurium and S. flexneri 21 . Sensing of L.
pneumophila flagellin which is secreted by the bacterial type IV secretion
system is mediated by NAIP5. Mutations affecting the NAIP5 locus (also
known as Birc1e) have been implicated in increased susceptibility of A/J
macrophages to infection with L. pneumophila. NAIP5 appears to form an
inflammasome complex containing IPAF (but not ASC) and Caspase-1 22 .
NAIP5-mediated signaling pathway and IPAF-mediated Caspase-1 activation
may act in concert to restrict L. pneumophila growth in macrophages 23,24 .
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