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.
Bibliographical noteFunding Information:
The authors thank Dong-Su Jang, MFA (Medical Illustrator, Medical Support Section, Yonsei University College of Medicine) for his help with the illustrations. They also thank Dr. Hyun Seok Kim (Yonsei University College of Medicine) for assistance with statistical analysis. This work was supported by National Research Foundation of Korea grants funded by the Korean Government (2014R1A4A1008625), and by the Bio & Medical Technology Development Program of the NRF funded by the Korean government, MSIP (2015M3A9B6073856).
© 2017 Yang, Lee, Park, Cho, Lee, Park, Shin, Son, Yoon and Yu.
- Bacterial secretant
- Pseudomonas aeruginosa
- Quorum sensing
ASJC Scopus subject areas
- Immunology and Allergy