Infection and Immunity, April 2000, p. 2237-2244, Vol. 68, No. 4
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Unité de Biologie des Interactions Cellulaires, CNRS URA 1960,1 Unité de Biologie Moléculaire du Gène,3 and Unité de Histopathologie,4 Institut Pasteur, 75724 Paris Cedex 15, France, and Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 722022
Received 8 July 1999/Returned for modification 16 August 1999/Accepted 13 December 1999
The pathology observed during Chlamydia infection is
due initially to localized tissue damage caused by the infection
itself, followed by deleterious host inflammatory responses that lead to permanent scarring. We have recently reported that the infection by
Chlamydia in vitro results in apoptosis of epithelial cells and macrophages and that infected monocytes secrete the proinflammatory cytokine interleukin-1
. At the same time, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-
) can also trigger
apoptosis of susceptible cells. To study the possible relationship
between Chlamydia trachomatis infection and apoptosis in
vivo, we used the terminal deoxynucleotidyltransferase-mediated dUTP
nick end labeling technique to determine whether infection may cause
apoptosis in the genital tract of mice and, conversely, whether
cytokines produced during the inflammatory response may modulate the
level of apoptosis. Our results demonstrate that infected cells in the endocervix at day 2 or 7 after infection are sometimes apoptotic, although there was not a statistically significant change in the number
of apoptotic cells in the endocervix. However, large clumps of
apoptotic infected cells were observed in the lumen, suggesting that
apoptotic cells may be shed from the endocervix. Moreover, there was a
large increase in the number of apoptotic cells in the uterine horns
and oviducts after 2 or 7 days of infection, which was accompanied by
obvious signs of upper tract pathology. Interestingly, depletion of
TNF-
led to a decrease in the level of apoptosis in the uterine
horns and oviducts of animals infected for 7 days, suggesting that the
inflammatory cytokines may exert part of their pathological effect via
apoptosis in infected tissues.
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