title: Bacterial Secretant fromPseudomonas aeruginosaDampens Inflammasome Activation in a Quorum Sensing-Dependent Manner.
abstract: Inflammasome signaling can contribute to host innate immune defense against bacterial pathogens such asPseudomonas 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 ofP. 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) fromP. aeruginosacan dampen host inflammasome signaling in mouse bone marrow-derived macrophages. We found that BS from QS-defective ΔlasR/rhlRmutant, 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/rhlRsecretant, 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 ofP. aeruginosafacilitates bacteria to evade host inflammasome-dependent sensing machinery.
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Jungmin
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Kang-Mu
authors.initials: KM
authors.lastname: Lee
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Sangjun
authors.initials: S
authors.lastname: Park
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea; Doping Control Center, Korea Institute of Science and Technology, Seoul, South Korea.
authors.forename: Yoeseph
authors.initials: Y
authors.lastname: Cho
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Eunju
authors.initials: E
authors.lastname: Lee
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University , Gwangju , South Korea.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Korea University Guro Hospital , Seoul , South Korea.
authors.forename: Ok Sarah
authors.initials: OS
authors.lastname: Shin
authors.affiliation: Doping Control Center, Korea Institute of Science and Technology , Seoul , South Korea.
authors.forename: Junghyun
authors.initials: J
authors.lastname: Son
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Sang Sun
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: Department of Microbiology and Immunology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine , Seoul , South Korea.
authors.forename: Je-Wook
authors.initials: JW
authors.lastname: Yu
keywords: Pseudomonas aeruginosa; bacterial secretant; flagellin; inflammasome; quorum sensing