Chlamydia pneumoniae secretion of a protease-like activity factor for degrading host cell transcription factors required for [correction of factors is required for] major histocompatibility complex antigen expression.
Chlamydia pneumoniae is a causative agent for many respiratory infections and has been associated with cardiovascular diseases in humans. The pathogenicity of C. pneumoniae is thought to depend on its ability to cause persistent infection and to evade host defense. Genome sequence analysis indicates that C. pneumoniae encodes a homologue of a chlamydial protease-like activity factor from C. trachomatis (CPAFct). We designated the C. pneumoniae homologue as CPAFcp. Recombinant CPAFcp was produced and found to degrade RFX5, a host transcription factor required for major histocompatibility complex (MHC) antigen expression. The degradation was inhibitable by lactacystin, an irreversible proteasome inhibitor. Furthermore, CPAFcp was secreted into host cytosol by C. pneumoniae organisms. Depletion of the C. pneumoniae-secreted CPAFcp with specific antibodies completely ablated the RFX5 degradation activity in the infected cells, suggesting that CPAFcp is necessary for the degradation of host transcription factors required for MHC antigen expression during C. pneumoniae infection. These observations have revealed a unique molecular mechanism for C. pneumoniae to evade host adaptive immunity that may aid in its persistence.
Fan
Peiyi
P
Department of Microbiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
Dong
Feng
F
Huang
Yanqing
Y
Zhong
Guangming
G
D000818:Animals; D016993:Chlamydophila pneumoniae / Q000201:enzymology* / Q000235:genetics; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D016680:Genome, Bacterial; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis*; D006801:Humans; D051379:Mice; D011817:Rabbits; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D000949:Histocompatibility Antigens Class II; C093524:RFX5 protein, human; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D010450:Endopeptidases; C425923:CPA factor