Modulation of Host Death by Chlamydia trachomatis : the Role of the Chlamydia-specific Protease CPAF

Yu, Hangxing

Chlamydia is confirmed to modulate host cell death pathways to complete its own developmental cycle. In this study, the effect of Chlamydia trachomatis on activation of host cell death pathways was investigated. C. trachomatis infection induced caspase-3-independent cell death. After Chlamydia infection, nuclear protein PARP-1 was cleaved to necrotic-like multi-fragment. This cleavage was accompanied by a highly decreased enzymatic activity. PARP-1 silencing by siRNA in the host cells resulted in cell death similar to that induced by Chlamydia infection. Chlamydial but not host cell protease contributed to this PARP-1 cleavage. The purified proteolytic protein fraction exhibited a 29 kDa fragment, which corresponds to the NH2-terminal portion of chlamydial proteolytic activity factor (CPAF). The high mobility group box-1 (HMGB-1) protein, which is known to be released to the extracellular matrix to induce inflammation during necrotic cell death, was also degraded by CPAF in the late stage of the chlamydial infectious cycle. This gives the suggestion that Chlamydia may evade the host immune system by degrading this inflammatory factor. Under the stressful conditions like exposure to IFN-γ, C. trachomatis underwent a special form so called “persistence”, with minimal cultivability and low infectivity. During persistent chlamydial infection, the nuclear proteins PARP-1 and HMGB-1 were not degraded, suggesting the CPAF translocation to the host nucleus was inhibited during persistence. Our results gave the convincible evidence that the Chlamydia-secreted protease CPAF plays an important role in the regulation of host cell death pathways. During active infection, it could cleave nuclear proteins and induce the host cell instability and subsequent cell death. For the long-term persistence in host cells, the nuclear translocation of CPAF was inhibited. The nuclear proteins could keep intact to make sure the stability of the host cells.

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Yu, Hangxing: Modulation of Host Death by Chlamydia trachomatis. the Role of the Chlamydia-specific Protease CPAF. 2010.

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