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Differential requirements for NAIP5 in activation of the NLRC4 inflammasome

Lightfield, Karla L ; Persson, Jenny LU ; Trinidad, Norver J ; Brubaker, Sky W ; Kofoed, Eric M ; Sauer, John-Demian ; Dunipace, Eric A ; Warren, Sarah E ; Miao, Edward A and Vance, Russell E (2011) In Infection and Immunity 79(4). p.14-1606
Abstract

Inflammasomes 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... (More)

Inflammasomes 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.

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; ; ; ; ; ; ; ; and
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Apoptosis Regulatory Proteins/immunology, Calcium-Binding Proteins/immunology, Cytotoxicity, Immunologic/immunology, Flagellin/immunology, Flow Cytometry, Immunity, Innate/immunology, Inflammasomes/immunology, Legionella pneumophila/immunology, Legionellosis/immunology, Macrophages/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Neuronal Apoptosis-Inhibitory Protein/immunology, Peptides/immunology, Reverse Transcriptase Polymerase Chain Reaction, Salmonella Infections, Animal/immunology, Salmonella typhimurium/immunology
in
Infection and Immunity
volume
79
issue
4
pages
9 pages
publisher
American Society for Microbiology
external identifiers
  • scopus:79953315378
  • pmid:21282416
ISSN
1098-5522
DOI
10.1128/IAI.01187-10
language
English
LU publication?
no
id
7ad59498-0766-4487-9f62-a60ab3e19f4d
date added to LUP
2019-05-21 09:06:11
date last changed
2020-08-12 08:39:31
@article{7ad59498-0766-4487-9f62-a60ab3e19f4d,
  abstract     = {<p>Inflammasomes 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.</p>},
  author       = {Lightfield, Karla L and Persson, Jenny and Trinidad, Norver J and Brubaker, Sky W and Kofoed, Eric M and Sauer, John-Demian and Dunipace, Eric A and Warren, Sarah E and Miao, Edward A and Vance, Russell E},
  issn         = {1098-5522},
  language     = {eng},
  number       = {4},
  pages        = {14--1606},
  publisher    = {American Society for Microbiology},
  series       = {Infection and Immunity},
  title        = {Differential requirements for NAIP5 in activation of the NLRC4 inflammasome},
  url          = {http://dx.doi.org/10.1128/IAI.01187-10},
  doi          = {10.1128/IAI.01187-10},
  volume       = {79},
  year         = {2011},
}