Bacterial secretant from Pseudomonas aeruginosa dampens inflammasome activation in a Quorum Sensing-dependent manner

Jungmin Yang, Kang Mu Lee, Sangjun Park, Yoeseph Cho, Eunju Lee, Jong Hwan Park, Ok Shin, Junghyun Son, Sang Sun Yoon, Je Wook Yu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Inflammasome signaling can contribute to host innate immune defense against bacterial pathogens such as Pseudomonas aeruginosa. However, bacterial evasion of host inflammasome activation is still poorly elucidated. Quorum sensing (QS) is a bacterial communication mechanism that promotes coordinated adaptation by triggering expression of a wide range of genes. QS is thought to strongly contribute to the virulence of P. aeruginosa, but the molecular impact of bacterial QS on host inflammasome defense is completely unknown. Here, we present evidence that QS-related factors of the bacterial secretant (BS) from P. aeruginosa can dampen host inflammasome signaling in mouse bone marrow-derived macrophages. We found that BS from QS-defective ΔlasR/rhlR mutant, but not from wild-type (WT) P. aeruginosa, induces robust activation of the NLRC4 inflammasome. P. aeruginosa-released flagellin mediates this inflammasome activation by ΔlasR/rhlR secretant, but QS-regulated bacterial proteases in the WT BS impair extracellular flagellin to attenuate NLRC4 inflammasome activation. P. aeruginosa-secreted proteases also degrade inflammasome components in the extracellular space to inhibit the propagation of inflammasome-mediated responses. Furthermore, QS-regulated virulence factor pyocyanin and QS autoinducer 3-oxo-C12-homoserine lactone directly suppressed NLRC4- and even NLRP3-mediated inflammasome assembly and activation. Taken together, our data indicate that QS system of P. aeruginosa facilitates bacteria to evade host inflammasome-dependent sensing machinery.

Original languageEnglish
Article number333
JournalFrontiers in Immunology
Volume8
Issue numberMAR
DOIs
Publication statusPublished - 2017 Mar 27

Keywords

  • Bacterial secretant
  • Flagellin
  • Inflammasome
  • Pseudomonas aeruginosa
  • Quorum sensing

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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