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Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.

Publication ,  Journal Article
Miao, EA; Mao, DP; Yudkovsky, N; Bonneau, R; Lorang, CG; Warren, SE; Leaf, IA; Aderem, A
Published in: Proc Natl Acad Sci U S A
February 16, 2010

The mammalian innate immune system uses Toll-like receptors (TLRs) and Nod-LRRs (NLRs) to detect microbial components during infection. Often these molecules work in concert; for example, the TLRs can stimulate the production of the proforms of the cytokines IL-1beta and IL-18, whereas certain NLRs trigger their subsequent proteolytic processing via caspase 1. Gram-negative bacteria use type III secretion systems (T3SS) to deliver virulence factors to the cytosol of host cells, where they modulate cell physiology to favor the pathogen. We show here that NLRC4/Ipaf detects the basal body rod component of the T3SS apparatus (rod protein) from S. typhimurium (PrgJ), Burkholderia pseudomallei (BsaK), Escherichia coli (EprJ and EscI), Shigella flexneri (MxiI), and Pseudomonas aeruginosa (PscI). These rod proteins share a sequence motif that is essential for detection by NLRC4; a similar motif is found in flagellin that is also detected by NLRC4. S. typhimurium has two T3SS: Salmonella pathogenicity island-1 (SPI1), which encodes the rod protein PrgJ, and SPI2, which encodes the rod protein SsaI. Although PrgJ is detected by NLRC4, SsaI is not, and this evasion is required for virulence in mice. The detection of a conserved component of the T3SS apparatus enables innate immune responses to virulent bacteria through a single pathway, a strategy that is divergent from that used by plants in which multiple NB-LRR proteins are used to detect T3SS effectors or their effects on cells. Furthermore, the specific detection of the virulence machinery permits the discrimination between pathogenic and nonpathogenic bacteria.

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 16, 2010

Volume

107

Issue

7

Start / End Page

3076 / 3080

Location

United States

Related Subject Headings

  • Transfection
  • Protein Conformation
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Immunity, Innate
  • Caspase 1
  • Calcium-Binding Proteins
  • Bacterial Proteins
 

Citation

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Miao, E. A., Mao, D. P., Yudkovsky, N., Bonneau, R., Lorang, C. G., Warren, S. E., … Aderem, A. (2010). Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A, 107(7), 3076–3080. https://doi.org/10.1073/pnas.0913087107
Miao, Edward A., Dat P. Mao, Natalya Yudkovsky, Richard Bonneau, Cynthia G. Lorang, Sarah E. Warren, Irina A. Leaf, and Alan Aderem. “Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.Proc Natl Acad Sci U S A 107, no. 7 (February 16, 2010): 3076–80. https://doi.org/10.1073/pnas.0913087107.
Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, et al. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3076–80.
Miao, Edward A., et al. “Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome.Proc Natl Acad Sci U S A, vol. 107, no. 7, Feb. 2010, pp. 3076–80. Pubmed, doi:10.1073/pnas.0913087107.
Miao EA, Mao DP, Yudkovsky N, Bonneau R, Lorang CG, Warren SE, Leaf IA, Aderem A. Innate immune detection of the type III secretion apparatus through the NLRC4 inflammasome. Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3076–3080.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

February 16, 2010

Volume

107

Issue

7

Start / End Page

3076 / 3080

Location

United States

Related Subject Headings

  • Transfection
  • Protein Conformation
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Membrane Proteins
  • Immunity, Innate
  • Caspase 1
  • Calcium-Binding Proteins
  • Bacterial Proteins