The Journal of Immunology, 1998, 161: 4220-4226.
Copyright © 1998 by The American Association of Immunologists
Apoptosis of Epithelial Cells and Macrophages Due to Infection with the Obligate Intracellular Pathogen Chlamydia psittaci1
David M. Ojcius2,
Philippe Souque,
Jean-Luc Perfettini and
Alice Dautry-Varsat
Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique 1960, Institut Pasteur, Paris, France
We have characterized the cytotoxic activity of the obligate
intracellular bacterium Chlamydia psittaci, which
resides within a membrane-bound vacuole during the 2-day infection
cycle. We have established that infected epithelial cells and
macrophages die through apoptosis, which is measurable within 1 day of
infection and requires productive infection by the bacteria. Inhibition
of host cell protein synthesis has no effect on cell death, but
blocking bacterial entry or bacterial protein synthesis prevents
apoptosis, implying that bacterial growth is required for death of the
host cell. Apoptosis was confirmed through the use of electron
microscopy, terminal deoxynucleotidyl transferase-mediated dUTP nick
end labeling, gel agarose electrophoresis of fragmented DNA, and
propidium-iodide labeling of host cell nuclei. Although infected cells
died preferentially, both infected and uninfected cells became
apoptotic, suggesting that the infected cells may secrete proapoptotic
factors. Inhibition of either of two proapoptotic enzymes, caspase-1 or
caspase-3, did not significantly affect
Chlamydia-induced apoptosis. These results suggest that,
as in the case of apoptosis due to Bax expression or oncogene
dysregulation, which initiate the apoptotic program within the cell
interior, the Chlamydia infection may trigger an
apoptotic pathway that is independent of known caspases. As apoptotic
cells secrete proinflammatory cytokines,
Chlamydia-induced apoptosis may contribute to the
inflammatory response of the host.
This Website Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 1998 by The American Association of Immunologists, Inc. All rights reserved.