Cleavage‐dependent activation of a chlamydia‐secreted protease

Dong, Feng; Pirbhai, Mustak; Zhong, Youmin; Zhong, Guangming

doi:10.1111/j.1365-2958.2004.04072.x

Cited by 44 publications

(66 citation statements)

References 24 publications

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“…Chlamydial proteins such as the secreted serine protease CPAF (24) can oligomerize. CPAF is synthesized as a proenzyme, and homodimerization of CPAF is necessary for acquiring proteolytic activity (17,18,24). However, it is not clear why Pgp3 trimerizes.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Pgp3, aChlamydia trachomatisPlasmid-Encoded Immunodominant Antigen

Chen¹,

Lei²,

Lu³

et al. 2010

J Bacteriol

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Human antibody recognition of Chlamydia trachomatis plasmid-encoded Pgp3 protein is dependent on the native conformation of Pgp3. The structural basis for the conformation dependence and the function of Pgp3 remain unknown. Here, we report that Pgp3 trimerization is required for the recognition of Pgp3 by human antibodies. In a native polyacrylamide gel, Pgp3 purified from a bacterial expression system migrated as stable trimers that were dissociated into monomers only by treatment with urea or sodium dodecyl sulfate (SDS) but not nonionic detergents. Human antibodies recognized trimeric but not monomeric Pgp3, suggesting that Pgp3 is presented to the human immune system as trimers during C. trachomatis infection. The endogenous Pgp3 secreted into the chlamydial outer membrane complex or host cell cytosol is always trimerized. Intact Pgp3 trimers were eluted from the outer membrane complex by a combination of nonionic detergents with reducing agents but not by the presence of either alone. These observations have provided important information for further understanding the role of Pgp3 in chlamydial pathogenesis and potentially optimizing Pgp3 as a subunit vaccine candidate antigen.

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Section: Discussionmentioning

confidence: 99%

Characterization of Pgp3, aChlamydia trachomatisPlasmid-Encoded Immunodominant Antigen

Chen¹,

Lei²,

Lu³

et al. 2010

J Bacteriol

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“…Members of our laboratory have recently identified a chlamydia-secreted protein, designated chlamydial proteasome/protease-like activity factor (CPAF), in the cytosol of the chlamydia-infected cells (38). CPAF is synthesized as a proenzyme and processed to form a functional intramolecular dimer (8,9,38). Most importantly, CPAF is both necessary and sufficient for degrading the host transcriptional factors RFX5 and USF-1, required for MHC gene activation (38), which may provide a molecular explanation for chlamydia-induced inhibition of MHC antigens.…”

mentioning

confidence: 99%

Human Antibody Responses to a Chlamydia-Secreted Protease Factor

Sharma¹,

Bosnic²,

Piper

et al. 2004

Infect Immun

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We have previously identified a chlamydia-secreted protein (designated chlamydial proteasome/protease-like activity factor, or CPAF) in the cytosol of chlamydia-infected cells. Although CPAF is known to degrade host transcription factors required for major histocompatibility complex antigen expression in cultured cells, it is not clear whether CPAF is produced and maintains similar functions in humans infected with chlamydial organisms. We now report that CPAF does not preexist in chlamydial organisms and that CPAF synthesis requires live organism replication in cultured cells. Mice inoculated with live, but not mice inoculated with dead, chlamydial organisms produced a strong antibody response to CPAF, correlating CPAF-specific antibody production with CPAF synthesis in animals. Sera from women diagnosed with Chlamydia trachomatis cervicitis displayed higher levels of antibodies to CPAF than to either chlamydial major outer membrane protein or heat shock protein 60, suggesting that CPAF is both produced and immunogenic during human chlamydial infection.

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“…In this study, we used chlamydial protease-like activity factor (CPAF) 4 (23)(24)(25)(26)(27)(28)(29), a chlamydial vaccine Ag that induces protective immunity in a CD4…”

mentioning

confidence: 99%

Antigen-Specific CD4+ T Cells Produce Sufficient IFN-γ to Mediate Robust Protective Immunity against Genital Chlamydia muridarum Infection

Murthy

Guentzel

et al. 2008

The Journal of Immunology

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Chlamydia has been shown to evade host-specific IFN-γ-mediated bacterial killing; however, IFN-γ-deficient mice exhibit suboptimal late phase vaginal Chlamydia muridarum clearance, greater dissemination, and oviduct pathology. These findings introduce constraints in understanding results from murine chlamydial vaccination studies in context of potential implications to humans. In this study, we used mice deficient in either IFN-γ or the IFN-γ receptor for intranasal vaccination with a defined secreted chlamydial Ag, chlamydial protease-like activity factor (CPAF), plus CpG and examined the role of IFN-γ derived from adoptively transferred Ag-specific CD4+ T cells in protective immunity against genital C. muridarum infection. We found that early Ag-specific IFN-γ induction and CD4+ T cell infiltration correlates with the onset of genital chlamydial clearance. Adoptively transferred IFN-γ competent CPAF-specific CD4+ T cells failed to enhance the resolution of genital chlamydial infection within recipient IFN-γ receptor-deficient mice. Conversely, IFN-γ production from adoptively transferred CPAF-specific CD4+ T cells was sufficient in IFN-γ-deficient mice to induce early resolution of infection and reduction of subsequent pathology. These results provide the first direct evidence that enhanced anti-C. muridarum protective immunity induced by Ag-specific CD4+ T cells is dependent upon IFN-γ signaling and that such cells produce sufficient IFN-γ to mediate the protective effects. Additionally, MHC class II pathway was sufficient for induction of robust protective anti-C. muridarum immunity. Thus, targeting soluble candidate Ags via MHC class II to CD4+ T cells may be a viable vaccine strategy to induce optimal IFN-γ production for effective protective immunity against human genital chlamydial infection.

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Cleavage‐dependent activation of a chlamydia‐secreted protease

Cited by 44 publications

References 24 publications

Characterization of Pgp3, aChlamydia trachomatisPlasmid-Encoded Immunodominant Antigen

Characterization of Pgp3, aChlamydia trachomatisPlasmid-Encoded Immunodominant Antigen

Human Antibody Responses to a Chlamydia-Secreted Protease Factor

Antigen-Specific CD4+ T Cells Produce Sufficient IFN-γ to Mediate Robust Protective Immunity against Genital Chlamydia muridarum Infection

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