A protein secreted by the respiratory pathogen Chlamydia pneumoniae impairs IL-17 signalling via interaction with human Act1.
Chlamydia pneumoniae is a common respiratory pathogen that has been associated with a variety of chronic diseases including asthma and atherosclerosis. Chlamydiae are obligate intracellular parasites that primarily infect epithelial cells where they develop within a membrane-bound vacuole, termed an inclusion. Interactions between the microorganism and eukaryotic cell can be mediated by chlamydial proteins inserted into the inclusion membrane. We describe here a novel C. pneumoniae-specific inclusion membrane protein (Inc) CP0236, which contains domains exposed to the host cytoplasm. We demonstrate that, in a yeast two-hybrid screen, CP0236 interacts with the NFκB activator 1 (Act1) and this interaction was confirmed in HeLa 229 cells where ectopically expressed CP0236 was co-immunoprecipitated with endogenous Act1. Furthermore, we demonstrate that Act1 displays an altered distribution in the cytoplasm of HeLa cells infected with C. pneumoniae where it associates with the chlamydial inclusion membrane. This sequestration of Act1 by chlamydiae inhibited recruitment of the protein to the interleukin-17 (IL-17) receptor upon stimulation of C. pneumoniae-infected cells with IL-17A. Such inhibition of the IL-17 signalling pathway led to protection of Chlamydia-infected cells from NFκB activation in IL-17-stimulated cells. We describe here a unique strategy employed by C. pneumoniae to achieve inhibition of NFκB activation via interaction of CP0236 with mammalian Act1.
Wolf
Katerina
K
Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33101, USA.
Plano
Gregory V
GV
Fields
Kenneth A
KA
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D006367:HeLa Cells; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D001426:Bacterial Proteins; D020381:Interleukin-17; D008565:Membrane Proteins; D016328:NF-kappa B; C414202:TRAF3IP2 protein, human; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins