Abstract
Chlamydia is an obligate intracellular bacterial pathogen that replicates solely within a membrane-bound vacuole termed an inclusion. Chlamydia seems to perturb multiple cellular processes of the host, such as, rearrangement of the membrane trafficking system for its intracellular multiplication, and inhibition of host cell apoptosis for persistent infection. In an attempt to clarify host factor involvement in apoptosis regulation, we found that inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells. These opposition contributions to the chlamydial infection were confirmed using caspase-9−/− and apaf-1−/− MEFs. Similar phenomena also appeared in the case of infection with Chlamydia trachomatis. Interestingly, caspase-9 in apaf-1−/− MEFs was activated by chlamydial infection but during the infection caspase-3 was not activated. That is, caspase-9 was activated without support for multiplication and activation by Apaf-1, and the activated caspase-9 may be physically disconnected from the caspase cascade. This may be partially explained by the observation of caspase-9 accumulation within chlamydial inclusions. The sequestration of caspase-9 by chlamydia seems to result in apoptosis repression, which is crucial for the chlamydial development cycle. Because Apaf-1 shares domains with intracellular innate immune receptor NOD1, it may play a key role in the strategy to regulate chlamydial infection.
Highlights
Apoptosis or programmed cell death is an active process of cellular suicide triggered by a variety of stresses and physiological stimuli for tissue development and homeostasis of organisms [1]
In an attempt to clarify host factor involvement in apoptosis regulation, we found that inhibition of Caspase-9 restricted, while Apaf-1 promoted, Chlamydia pneumoniae infection in HEp-2, HeLa, and mouse epithelial fibroblast (MEF) cells
Chlamydia pneumoniae-mediated blockage of STS-induced apoptosis was found at 48 hpi and this blockage ceased by 72 hpi (Fig. 1)
Summary
Apoptosis or programmed cell death is an active process of cellular suicide triggered by a variety of stresses and physiological stimuli for tissue development and homeostasis of organisms [1]. Apoptosis (2015) 20:1271–1280 caspase-3 activation leading to the apoptotic nuclear structure [4]. This apoptotic response is tightly regulated by Bcl-2 to prevent the release of cytochrome c from mitochondria [5]. Coping with defensive systems of host organisms as growth environments, intracellular bacteria, such as Shigella and Legionella, are thought to have developed a variety of strategies for modulating the apoptotic process in host cells, especially during early stages of the life cycle [7]
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