Unknown

Dataset Information

0

A novel pathway for inducible nitric-oxide synthase activation through inflammasomes.


ABSTRACT: Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1?/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to clear infections, little is known about the relative anti-pathogen effector mechanisms operating through each of them. Here we show that the cytosolic flagellin (FLA-BSDot) was able to activate iNOS, an enzyme previously associated with TLR5 pathway. Using Nlrc4- or Naip5-deficient macrophages, we found that both receptors are involved in iNOS activation by FLA-BSDot. Moreover, distinct from extracellular flagellin (FLA-BS), iNOS activation by intracellular flagellin is completely abrogated in the absence of caspase-1. Interestingly, IL-1? and IL-18 do not seem to be important for FLA-BSDot-mediated iNOS production. Together, our data defined an additional anti-pathogen effector mechanism operated through Naip5 and Nlrc4 inflammasomes and illustrated a novel signaling transduction pathway that activates iNOS.

SUBMITTER: Buzzo CL 

PROVIDER: S-EPMC2952210 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature

altmetric image

Publications


Innate immune recognition of flagellin is shared by transmembrane TLR5 and cytosolic Nlrc4 (NOD-like receptor family CARD (caspase activation recruitment domain) domain containing 4)/Naip5 (neuronal apoptosis inhibitory protein 5). TLR5 activates inflammatory genes through MYD88 pathway, whereas Nlrc4 and Naip5 assemble multiprotein complexes called inflammasomes, culminating in caspase-1 activation, IL-1β/IL-18 secretion, and pyroptosis. Although both TLR5 and Naip5/Nlrc4 pathways cooperate to  ...[more]

Similar Datasets

| S-EPMC5288713 | biostudies-literature
| S-EPMC2552398 | biostudies-literature
| S-EPMC4712158 | biostudies-literature
| S-EPMC3960077 | biostudies-literature
| S-EPMC3707674 | biostudies-literature
| S-EPMC4338739 | biostudies-literature
| S-EPMC6908786 | biostudies-literature
| S-EPMC4387900 | biostudies-literature
2015-02-02 | GSE65436 | GEO
| S-EPMC5485952 | biostudies-literature