Chlamydia trachomatis-infected host cells resist dsRNA-induced apoptosis

Abstract

Summary: Human pathogenic Chlamydia trachomatis have evolved sophisticated mechanisms to manipulate host cell signalling pathways in order to prevent apoptosis. We show here that host cells infected with C. trachomatis resist apoptosis induced by polyI:C, a synthetic double-stranded RNA that mimics viral infections. Infected cells displayed significantly reduced levels of PARP cleavage, caspase-3 activation and a decrease in the TUNEL positive population in the presence of polyI:C. Interestingly, the chlamydial block of apoptosis was upstream of the initiator caspase-8. Processing of caspase-8 was reduced in infected cells and coincided with a decrease in Bid truncation and downstream caspase-9 cleavage. Moreover, the enzymatic activity of caspase-8, measured by a luminescent substrate, was significantly reduced in infected cells. Caspase-8 inhibition by Chlamydia was dependent on cFlip as knock-down of cFlip decreased the chlamydial block of caspase-8 activation and consequently reduced apoptosis inhibition. Our data implicate that chlamydial infection interferes with the host cell's response to viral infections and thereby influences the fate of the cell. © 2010 Blackwell Publishing Ltd.