Differential requirements for NAIP5 in activation of the NLRC4 inflammasome

TitleDifferential requirements for NAIP5 in activation of the NLRC4 inflammasome
Publication TypeJournal Article
Year of Publication2011
AuthorsLightfield KL, Persson J, Trinidad NJ, Brubaker SW, Kofoed EM, Sauer JD, Dunipace EA, Warren SE, Miao EA, Vance RE
JournalInfect Immun
Volume79
Pagination1606-14
Date PublishedApr
PubMed Central IDPMC3067536
PMIDhttp://www.ncbi.nlm.nih.gov/pubmed/21282416
KeywordsAnimals, Apoptosis Regulatory Proteins/*immunology/metabolism, Calcium-Binding Proteins/*immunology/metabolism, Cytotoxicity, Immunologic/immunology, Flagellin/*immunology, Flow Cytometry, Immunity, Innate/*immunology, Inflammasomes/*immunology, Legionella pneumophila/immunology, Legionellosis/immunology, Macrophages/immunology/microbiology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuronal Apoptosis-Inhibitory Protein/*immunology/metabolism, Peptides/immunology, Reverse Transcriptase Polymerase Chain Reaction, Salmonella Infections, Animal/immunology, Salmonella typhimurium/immunology
AbstractInflammasomes are cytosolic multiprotein complexes that assemble in response to infectious or noxious stimuli and activate the CASPASE-1 protease. The inflammasome containing the nucleotide binding domain-leucine-rich repeat (NBD-LRR) protein NLRC4 (interleukin-converting enzyme protease-activating factor [IPAF]) responds to the cytosolic presence of bacterial proteins such as flagellin or the inner rod component of bacterial type III secretion systems (e.g., Salmonella PrgJ). In some instances, such as infection with Legionella pneumophila, the activation of the NLRC4 inflammasome requires the presence of a second NBD-LRR protein, NAIP5. NAIP5 also is required for NLRC4 activation by the minimal C-terminal flagellin peptide, which is sufficient to activate NLRC4. However, NLRC4 activation is not always dependent upon NAIP5. In this report, we define the molecular requirements for NAIP5 in the activation of the NLRC4 inflammasome. We demonstrate that the N terminus of flagellin can relieve the requirement for NAIP5 during the activation of the NLRC4 inflammasome. We also demonstrate that NLRC4 responds to the Salmonella protein PrgJ independently of NAIP5. Our results indicate that NAIP5 regulates the apparent specificity of the NLRC4 inflammasome for distinct bacterial ligands.

Back