Cirtical role for Salmonella effector SopB in regulating inflammasome activation |
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| Institution: | 1. Key Laboratory of Zoonosis, Ministry of Education, College of Animal Medicine, Jilin University, Changchun 130062, China;2. Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada;3. From the Section of Microbiology and;4. Department of Life Sciences, MRC Centre for Molecular Bacteriology and Infection, Imperial College London, London SW7 2AZ, United Kingdom and;5. the Division of Protein and Nucleic Acid Chemistry, MRC Laboratory of Molecular Biology, Cambridge CB2 OQH, United Kingdom;1. Instituto de Investigaciones en Microbiología y Parasitología Médica, Universidad de Buenos Aires-Consejo Nacional de Investigaciones Científicas y Técnicas (IMPaM, UBA-CONICET), Facultad de Medicina, Paraguay 2155, p12, C1121ABG, Buenos Aires, Argentina;2. Centro de Virología Animal, Instituto de Ciencia y Tecnología Dr. Cesar Milstein CONICET, Saladillo 2468, C1440FFX, Buenos Aires, Argentina;3. From the Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany,;4. the Max von Pettenkofer Institute for Hygiene and Medical Microbiology, Ludwig Maximilians University, 80336 Munich, Germany,;5. the Institute of Genetics, University of Bonn, D-53127 Bonn, Germany, and;6. the Helmholtz Centre for Infection Research (HZI), 38124 Braunschweig, Germany;1. College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China;2. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan 611130, PR China |
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| Abstract: | ObjectiveSalmonella is known to evolve many mechanisms to avoid or delay inflammasome activation which remain largely unknown. In this study, we investigated whether the SopB protein critical to bacteria virulence capacity was an effector that involved in the regulation of inflammasome activation.MethodsBMDMs from NLRC4-, NLRP3-, caspase-1/-11-, IFI16- and AIM2-deficient mice were pretreated with LPS, and subsequently stimulated with a series of SopB-related strains of Salmonella, inflammasome induced cell death, IL-1β secretion, cleaved caspase-1 production and ASC speckle formation were detected.ResultsWe found that SopB could inhibit host IL-1β secretion, caspase-1 activation and inflammasome induced cell death using a series of SopB-related strains of Salmonella; however the reduction of IL-1β secretion was not dependent on sensor that contain PYD domain, such as NLRP3, AIM2 or IFI16, but dependent on NLRC4. Notably, SopB specifically prevented ASC oligomerization and the enzymatic activity of SopB was responsible for the inflammasome inhibition. Furthermore, inhibition of Akt signaling induced enhanced inflammasome activation.ConclusionsThese results revealed a novel role in inhibition of NLRC4 inflammasome for Salmonella effector SopB. |
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| Keywords: | SopB Inflammasome activation NLRC4 Phosphatase activity |
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