Rac1 regulates the NLRP3 inflammasome which mediates IL-1beta production in Chlamydophila pneumoniae infected human mononuclear cells

• Published in: PloS one 2012-01, Vol.7 (1), p.e30379-e30379
• Main Authors: Eitel, Julia, Meixenberger, Karolin, van Laak, Claudia, Orlovski, Christine, Hocke, Andreas, Schmeck, Bernd, Hippenstiel, Stefan, N'Guessan, Philippe Dje, Suttorp, Norbert, Opitz, Bastian
• Format: Article
• Language: English
• Subjects: Adapters; Animals; Arteriosclerosis; Asthma; Atherosclerosis; Biology; Carrier Proteins - genetics; Carrier Proteins - metabolism; Caspase; Caspase-1; Cell Line; Chlamydia; Chlamydia pneumoniae; Chlamydia trachomatis; Chlamydophila pneumoniae; Chlamydophila pneumoniae - immunology; Chlamydophila pneumoniae - physiology; Committees; Cytokines; Enzyme-Linked Immunosorbent Assay; Ethics; Experiments; Gene expression; Guanosine triphosphatases; Guanosinetriphosphatase; Health aspects; Helicobacter pylori; Humans; Infections; Infectious diseases; Inflammasomes; Inflammasomes - metabolism; Inflammation; Interleukin 1; Interleukin-1beta - metabolism; Internal medicine; Laboratory animals; Leukocytes (mononuclear); Medicine; Mice; Mice, Inbred C57BL; Mice, Knockout; Monocytes - immunology; Monocytes - metabolism; Monocytes - microbiology; NLR Family, Pyrin Domain-Containing 3 Protein; Pathogens; Pneumonia; Polymerase Chain Reaction; Proteins; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Rac1 protein; Respiratory tract; Respiratory tract diseases; RNA Interference; siRNA; Transcription; Yersinia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0030379

Chlamydophila pneumoniae causes acute respiratory tract infections and has been associated with development of asthma and atherosclerosis. The production of IL-1β, a key mediator of acute and chronic inflammation, is regulated on a transcriptional level and additionally on a posttranslational level by inflammasomes. In the present study we show that C. pneumoniae-infected human mononuclear cells produce IL-1β protein depending on an inflammasome consisting of NLRP3, the adapter protein ASC and caspase-1. We further found that the small GTPase Rac1 is activated in C. pneumoniae-infected cells. Importantly, studies with specific inhibitors as well as siRNA show that Rac1 regulates inflammasome activation in C. pneumoniae-infected cells. In conclusion, C. pneumoniae infection of mononuclear cells stimulates IL-1β production dependent on a NLRP3 inflammasome-mediated processing of proIL-1β which is controlled by Rac1.