Cleavage of Host Keratin 8 by a Chlamydia-Secreted Protease

Dong, Feng; Su, Heng; Huang, Yanqing; Zhong, Youmin; Zhong, Guangming

doi:10.1128/iai.72.7.3863-3868.2004

Cited by 81 publications

(100 citation statements)

References 34 publications

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“…However, it has also been suggested that C. trachomatis may degrade host proteins to ensure a steady supply of amino acid building blocks for continued synthesis of bacterial proteins during infection (9). Regardless of the purpose, the proteolysis of host factors by C. trachomatis appears to promote a safe, nutrient-rich environmental niche for the bacteria to grow and replicate.…”

Section: Discussionmentioning

confidence: 99%

“…Likewise, degradation of the BH3 (Bcl-2 homology domain 3) family of proapoptotic factors protects C. trachomatis-infected cells from programmed cell death (8,12,41). Finally, C. trachomatis also cleaves host keratin 8, a subunit of intermediate filaments (9). Disruption of this component of the host cytoskeletal network has been postulated to allow the C. trachomatis vacuole to expand during infection.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to cyclin B1, several other host proteins have been reported to undergo proteolytic cleavage in response to C. trachomatis infection (8,9,12,41,45,46). Degradation of the transcription factors RFX5 and USF-1 during C. trachomatis infection has been shown to reduce expression of the major histocompatibility complex genes and thereby serve as a putative immune evasion strategy (45,46).…”

Section: Discussionmentioning

confidence: 99%

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Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

et al. 2006

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The obligate intracellular pathogen Chlamydia trachomatis interferes with a number of host cell processes, including cytoskeletal organization, vesicular trafficking, and apoptosis. In this study we report that C. trachomatisinfected cells proliferate more slowly than uninfected cells, suggesting that C. trachomatis may also manipulate the eukaryotic cell cycle. We further demonstrate that C. trachomatis infection destabilizes specific cell cycle proteins involved in the G 2 /M transition. C. trachomatis-infected cells, compared to uninfected cells, have lower levels of cyclin-dependent kinase 1. Additionally, C. trachomatis infection induces an N-terminal truncation of the mitotic cyclin B1. Manipulation of the host cell cycle may represent a strategy used by C. trachomatis to ensure a stable environment conducive to bacterial growth and replication.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

et al. 2006

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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…”

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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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“…Initially identified as a serine protease, multiple substrates for CPAF have been identified by, including the cellular proteins RFX5 [25], USF-1 [53], Keratin-8 [54], Keratin-18 [55], and the chlamydial proteins CPAF [56], CT005 [57], IncD [57], and TARP [57]. However, caution should be taken when analyzing these results since many substrates were proven to be artificial during cell processing after lysis of infected cells, which did not actually appear during chlamydial infection in vivo.…”

Section: Discussionmentioning

confidence: 99%

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

Zhang

Zhong

Cai

et al. 2017

J Infect Dev Ctries

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Introduction: Chlamydia trachomatis is the leading cause of sexually transmitted bacterial disease, which may cause significant threats, such as pelvic inflammatory disease and tubal factor infertility, to women if untreated. The pathological mechanisms of chlamydia-induced disease remain largely unknown, but it has been proposed that CPAF, a chlamydia-secreted serine protease, may play major roles in aiding chlamydial infection and contribute to chlamydia pathogenesis during in vivo infection. According to previous results, CPAF targets host immunity by degrading antimicrobial peptides and neutralizing complement activity; however, whether CPAF is involved in chlamydial antigen presentation has never been reported. Methodology: Antigen presentation assay was used to monitor the effects of CPAF on OT1-, OT2-, and chlamydia T cell antigen-mediated antigen presentation. In vitro cell-free degradation assay was used to detect CPAF processing of chlamydia T cell antigens. Results: We found that CPAF preferably inhibits OT2-but not OT1-mediated antigen presentation. CPAF inhibits OT2 antigen presentation by direct proteolytic cleavage in the wild type CPAF, but not enzymatic mutants. Importantly, several previously identified chlamydial T cell antigens were selectively degraded by CPAF when co-incubated in vitro. In addition, specific inhibition T cell antigen presentation by CPAF was correlated with T cell antigen cleavage by CPAF in vitro assay. Conclusions: Our experiments demonstrated that CPAF selectively and specifically degrades chlamydial T cell antigens, which chlamydia may utilize as a novel mechanism for evading host immune responses to promote chlamydia survival.

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Cleavage of Host Keratin 8 by a Chlamydia-Secreted Protease

Cited by 81 publications

References 34 publications

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

Chlamydia trachomatis Infection Induces Cleavage of the Mitotic Cyclin B1

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

CPAF selectively degrades chlamydial T cell antigens for inhibiting antigen presentation

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