| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Unité de Biologie des Interactions Cellulaires, Centre National de la Recherche Scientifique 1960, Institut Pasteur, Paris, France
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
and the Fas ligand) acting
via cell surface receptors (2), but is also associated with a number of
pathologic disorders, including AIDS, fulminant hepatitis, cancer, and
neurodegenerative disorders (4). The salient features of apoptosis are
membrane blebbing, cell shrinkage, chromatin condensation, and DNA
fragmentation. At later stages of apoptosis, the doomed cell fragments
into membrane-bound vesicles that are rapidly ingested by neighboring
cells (1). Microbe-induced apoptosis was first identified for viral infections and has subsequently been reported in cases of infections with a large number of pathogenic bacteria and parasites (4, 5, 6, 7). Most of the latter studies report that infection of macrophages results in apoptosis, although occasionally infection has been found to inhibit apoptosis induced by other triggers (8, 9, 10). The ability of pathogens to induce apoptosis may play a role in the initiation of the infection, survival of the pathogens, and escape from the host immune response, as well as promoting inflammatory responses. For some pathogens, triggering of apoptosis may be a host response to reduce or inhibit microbial replication (5, 11, 12, 13).
Cytotoxicity due to infection by human and nonhuman strains of the intracellular bacteria Chlamydia has been reported for many years (14, 15, 16, 17, 18, 19, 20, 21), but the mechanism of cell death has not been investigated. Chlamydia species are among the most successful pathogens on earth, being causative agents of conjunctivitis, trachoma, pneumonia, and the most common sexually transmitted bacterial infections (22, 23, 24). For all of these Chlamydia species, the main pathologic response during the early part of the infection process is due to the acute inflammatory response by the host (25).
Macrophages and monocytes undergoing apoptosis have been found to
secrete the proinflammatory cytokine IL-1ß (26). Given the potential
role that Chlamydia-induced apoptosis may play during onset
of the inflammatory response, we investigated apoptosis in macrophages
and monocytes, in which infection has been described (27), and
epithelial cells, which represent the preferential target cells for
Chlamydia infection in vivo (25, 28). In epithelial cells,
infectious elementary bodies
(EB)3 are internalized into
vacuoles that avoid fusion with host cell lysosomes. After 6–10 h, the
EBs differentiate into noninfectious but metabolically active
reticulate bodies (RBs), which proliferate within the expanding
vacuole, giving rise to 1000 or more progeny per host cell. The
infection cycle ends after 
2 days, when RBs differentiate back to
EBs, the bacteria are released through a poorly characterized process,
and a new infection cycle begins (28).
A salient property of apoptotic cells is their detachment from neighboring cells, followed by removal by scavenger phagocytes (1); in vitro, apoptotic cells detach from growth substrate. We have found that many epithelial cells and macrophages are located in the supernatant after infection with Chlamydia psittaci, and that the cells display characteristic features of apoptosis. Infection-mediated apoptosis has been confirmed with several techniques including electron microscopy, which shows the morphologic changes associated with apoptosis; the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method, which reveals early DNA breaks during apoptosis; gel agarose electrophoresis, showing host cell DNA fragmentation due to infection; and nuclear staining with propidium iodide (PI), which allows for quantitation of apoptosis under different conditions. Results with inactivation of bacteria or inhibition of bacterial adhesion imply that a productive infection is required for apoptosis, which is measurable after a 1-day infection and increases afterward. Since both infected and uninfected cells become apoptotic, secreted factors from infected cells may also trigger apoptosis of uninfected cells. Cells undergoing apoptosis may thus secrete cytokines that contribute to the inflammatory response to Chlamydia infection.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The human cervical adenocarcinoma cell line, HeLa 229, the mouse macrophage cell line, J774, and Jurkat cells were from American Type Culture Collection (Manassas, VA). The THP1 cells (29) have been previously described. The cells were maintained at 37°C in an atmosphere of 5% CO2 in DMEM (Life Technologies, Rockville, MD) (for HeLa) or RPMI 1640 (for J774, Jurkat, and THP1) supplemented with 10% heat-inactivated FBS (Life Technologies) and 2 mM L-glutamine. The Chlamydia strain used here, the guinea pig inclusion conjunctivitis serovar of C. psittaci (25), was obtained from Dr. Roger Rank (University of Arkansas, Little Rock, AR).
DABCO (1,4-diazalbicyclo[2.2.2]octane), chloramphenicol, and heparin were from Sigma (St. Louis, MO), and Mowiol, the IL-1ß-converting enzyme (ICE; caspase-1) inhibitor II (Ac-YVAD-CMK), and the CPP32/apopain (caspase-3) inhibitor II (Z-DEVD-FMK) were from Calbiochem (La Jolla, CA). Texas Red-coupled F(ab')2 fragment goat anti-mouse Ig were purchased from Molecular Probes (Eugene, OR). The mAb against human Fas (clone CH-11) was from Upstate Biotechnology (Lake Placid, NY), and unconjugated and FITC-labeled anti-Chlamydia mAb were from Argene (Varilhes, France). RNase A (DNase free) was from Boehringer Mannheim (Meylan, France).
Preparation of Chlamydia and infection of host cells
The chlamydiae were grown in infected HeLa cell monolayer cultures as described (30). For infections, adherent HeLa and J774 cells were typically grown on coverslips or on 75-cm2 tissue culture flasks (Costar) until 60 to 70% confluence was obtained, then incubated with chlamydiae in cell culture medium for the indicated times at 37°C in 5% CO2. THP1 cells were infected in suspension in culture medium (29). Unless indicated otherwise, the Chlamydia was used at a multiplicity of infection (m.o.i.) between 1.0 and 2.0.
Confocal microscopy
Samples for confocal microscopy were fixed with paraformaldehyde, incubated with Abs, and mounted as previously described (31, 32). Apoptotic HeLa cells on coverslips were detected by enzymatic labeling of DNA strand breaks with the TUNEL technique (33) using the cell death detection kit from Boehringer Mannheim, following the manufacturer’s instructions. For these experiments, infected cells were fixed as described above, and apoptotic cells were detected as green (due to fluorescein-12-dUTP). Cells infected with Chlamydia were identified by revealing with unconjugated anti-Chlamydia mAb (1:500), followed by incubation with Texas Red-labeled anti-mouse Ig polyclonal Ab.
Fluorescently labeled samples were examined with a Leica confocal microscope (Heidelberg, Germany) attached to a diaplan microscope equipped with a double argon-krypton laser. Serial optical sections were typically recorded at 0.5-µm intervals with 63x and 100x lenses.
Cytofluorometry analysis of apoptosis
Quantitative measurements of apoptosis were performed by cytofluorometry of detergent-permeabilized PI-stained cells as described (34). Cells were first fixed with paraformaldehyde, and bacteria were revealed with FITC-labeled anti-Chlamydia mAb (1:500) before incubating with the PI buffer. Cytotoxicity was measured using the standard PI-exclusion assay with unpermeabilized cells. Unless noted otherwise, both adherent cells and cells in the supernatant were collected for analysis.
The cells were transferred into 12 x 75 mm Falcon 2052 FACS tubes (Becton Dickinson, San Jose, CA). Data from 10,000 HeLa cells were collected on a FACScan flow cytometer (Becton Dickinson) with an argon laser tuned to 488 nm.
Inhibition of apoptosis and Chlamydia adherence by heparin was measured with either HeLa or J774 that had been incubated with bacteria and 120 µg/ml of heparin (32). The bacteria were incubated in the heparin solutions in PBS for 1 h at 4°C before adding the mixture to an equivalent volume of HeLa or J774 cells in culture medium. After an hour, unbound bacteria were removed by washing once with PBS and replacing the supernatant with culture medium. After an additional 48 h, the percentage of apoptotic cells was determined by cytofluorometry. For UV inactivation experiments, the bacteria were exposed to UV light in a cell culture hood under constant stirring in an ice cold water bath for 60 min. For caspase or chloramphenicol inhibition experiments, 50 µM of the caspase-1 or caspase-3 inhibitor or 68 µg/ml chloramphenicol was maintained with the HeLa cells during the duration of the infection.
DNA fragmentation assay
HeLa or J774 cells (1–3 x 106) were washed
with PBS and centrifuged (270 x g for 5 min), and the
pellet was lysed with 0.6% SDS, 10 mM EDTA, 10 mM Tris, and 20 µg/ml
RNase A, pH 7.5, for 1 h at 37°C in 3 ml. Three hundred
microliters of 5 M NaCl was then added, and the preparation was
incubated for 1 h on ice and finally centrifigued for 30 min at
13,000 x g. The supernatant, containing the DNA, was
extracted with phenol-chloroform-isoamyl alcohol (25:24:1), and
low-m.w. DNA was precipitated with ethanol. Samples (3 µg DNA per
lane) were separated by electrophoresis on a 1.5% agarose gel and
visualized by ethidium bromide staining. UV or heparin inhibition
experiments were performed as above.
Electron microscopy
HeLa cells infected with chlamydiae for 0 h or 24 h were fixed with 2.5% glutaraldehyde for at least 2 h at room temperature. The fixed cells were then prepared for electron microscopy as previously described (30). Thin sections were poststained with uranyl acetate and lead citrate for examination on a Zeiss electron microscope at an accelerating voltage of 50 kV.
Measurement of IL-1ß secretion
Secretion of IL-1ß from HeLa and THP1 cells was measured using the Genzyme (Cambridge, MA) human IL-1ß ELISA kit following the manufacturer’s instructions. Cells were incubated with chlamydiae at an m.o.i. of 1.0 for 1 day. The supernatant was collected, centrifuged in Eppendorf tubes to remove cellular debris, and kept frozen at -80°C until ready for use. Supernatants were diluted in the ELISA kit wash buffer, and the absolute concentrations of IL-1ß were obtained by calibrating the ELISA kit with a known concentration of IL-1ß provided by the manufacturer.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
To characterize the cell death caused by C. psittaci,
we infected the HeLa cell line (derived from epithelial cells) and
measured the percentage of apoptotic cells by cytofluorometry, as
described in Materials and Methods. Concomitantly, we
measured the extent of overall cytotoxicity by the standard PI
exclusion method. As apoptotic cells detach from neighboring cells (1),
we first determined whether apoptotic cells appearing during infection
were located among the adherent cells or the cells in suspension. As
almost all apoptotic cells were in suspension (not shown), both
adherent cells and cells in suspension were collected for subsequent
analysis. Figure 1
shows the dependence
of cytotoxicity and apoptosis on the concentration of
Chlamydia used to infect the cells. After a 48-h infection,
almost half of the cells had died when infected with an m.o.i. of 1.0,
and most of the cells died after infection with an m.o.i. of 2.0. At
all of the bacterial dilutions used, most of the cytotoxicity was due
to apoptosis (Fig. 1).
|
). Similarly, to determine whether the chlamydiae need to invade
the host cell, we preincubated viable chlamydiae with 120 µg/ml
heparin, which has previously been shown to inhibit
Chlamydia adherence and infection of epithelial cells (32, 37, 38). Again, only background levels of cytotoxicity and apoptosis
were observed when cells were incubated for 48 h with chlamydiae
under these conditions (Fig. 1). Taken together, these results
demonstrate that Chlamydia induces apoptosis of epithelial
cells; the cells undergo apoptosis only if they have been productively
infected.
Depending on the Chlamydia strain and source of host cells,
Chlamydia can also infect most macrophages and monocytes
tested (27). To determine whether Chlamydia-induced
apoptosis is specific to epithelial cells, we also studied the effects
of the infection on the macrophage cell line J774 and on the monocytic
cell line THP1. Incubation with C. psittaci resulted in
apoptosis of both cell types, with a bacterial concentration dependence
similar to that observed for epithelial cells, although the percentage
of apoptotic macrophages or monocytes observed was lower than with HeLa
cells (shown for macrophages in Figure 2). Likewise, there was no apoptosis when
macrophages were incubated with UV-inactivated chlamydiae (not shown),
suggesting that an infection may be required for apoptosis.
|
). The extent of apoptosis then
increased rapidly, attaining approximately half of the cells after a
2-day infection. A similar time course was observed with macrophages,
although, consistent with Figure 3, the extent of apoptosis was always
lower than with epithelial cells (not shown).
|
To confirm that the cell death measured by cytofluorometry
corresponds to apoptosis, we characterized infected HeLa cells by
electron microscopy. Both adherent cells and cells in suspension were
collected for morphologic characterization (1, 3). While many
ostensibly healthy HeLa cells, containing large Chlamydia
inclusions, were observed after a 1-day infection (Fig. 4A), there were also many
condensed cells having distinctive features of apoptosis (Fig. 4, B–D). Thus, many cells displayed cell shrinkage, chromatin
condensation, and organelle dilatation (Fig. 4, B and
C), as well as more advanced signs of apoptosis, including
nuclear segmentation and cellular disintegration (Fig. 4D).
Many cells still associated with membrane-bound apoptotic bodies were
also observed (Fig. 4D).
|
). Entry of bacteria and a productive
infection was required for the fragmentation, since UV-inactivated
chlamydiae or chlamydiae that had been preincubated with heparin had a
much smaller effect (Fig. 5). Consistent with Figure 1, there was a low
level of DNA fragmentation in uninfected cells and cells incubated with
UV-inactivated bacteria or live bacteria and heparin (Fig. 5).
|
A), and both infected normal
cells and apoptotic cells that were not productively infected were
observed (Fig. 6B).
|
Effect of inhibitors on apoptosis
Since the eukaryotic cell protein synthesis inhibitor
cycloheximide inhibits many, but not all, types of apoptosis (3), we
evaluated by cytofluorometry whether cycloheximide had any effect on
Chlamydia-induced apoptosis. After a 48-h infection, there
was no significant effect of cycloheximide on
Chlamydia-induced apoptosis (Table I). As host cell protein synthesis played
no role in infection-mediated apoptosis, we tested whether
chloramphenicol, which inhibits protein synthesis by the chlamydiae
(39), has any effect. Most of the apoptosis was prevented by this
treatment (Table I).
|
).
As HeLa cells are not sensitive to Fas-mediated apoptosis in the
absence of cycloheximide, the activity of the caspase-3 inhibitor was
evaluated by measuring apoptosis of Jurkat cells incubated with
anti-Fas Ab. The caspase-3 inhibitor blocked essentially all of the
Fas-mediated apoptosis (Table I). The activity of the caspase-1
inhibitor was checked by infecting THP1 cells with C.
psittaci for 24 h and measuring the secretion of IL-1ß. It
has been previously reported that human monocytes incubated with
C. trachomatis secrete IL-1ß (44), and we have shown that
THP1 cells can be infected with C. psittaci (29). We
therefore measured IL-1ß secretion from THP1 cells after a 1-day
infection in the presence or absence of 50 µM of the caspase-1
inhibitor. While little if any IL-1ß was secreted from unstimulated
THP1 cells, incubation with C. psittaci caused a high level
of IL-1ß secretion, most of which could be blocked by including the
caspase-1 inhibitor in the medium (Table I).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1 day of infection (halfway through the
infection cycle), when the Chlamydia vacuole harbors
predominantly bacteria at the metabolically active RB developmental
stage. However, both infected and uninfected cells die through
apoptosis, suggesting that infected cells may also elaborate soluble
factors that induce apoptosis of neighboring uninfected cells. Apoptosis is mediated by highly specific enzymes known as caspases (40), which have a strong preference for Asp residues in the substrate sequence. Although caspase-1 (or ICE) is specific for the precursors of IL-1ß and IL-18 and is clearly involved in activation of proinflammatory cytokines, it remains to be seen whether caspase-1 is directly involved in executing the apoptotic program (43). Caspase-3 (CPP32, apopain), on the other hand, is clearly involved in promoting cell death (43). We have tested the effects of two inhibitors specific for caspase-1 and caspase-3. The caspase-1 inhibitor had no effect on Chlamydia-induced apoptosis, although it inhibited secretion of IL-1ß from monocytes infected with chlamydiae. To our initial surprise, the caspase-3 inhibitor also failed to diminish significantly the extent of apoptosis, implying that C. psittaci induces apoptosis through a pathway not dependent on caspase-3. These results are reminiscent of other recent reports showing caspase-independent apoptosis. In cells expressing the proapoptotic protein Bax, a caspase inhibitor failed to inhibit Bax-induced apoptosis (45, 46, 47), although it could still inhibit apoptosis triggered by Fas (45), suggesting that known caspases are not involved in Bax-induced apoptosis. Similarly, caspase inhibitors delay but do not prevent apoptosis induced by deregulated oncogenes and DNA damage (47). It has been proposed that, unlike apoptosis initiated by Fas, whose first signal is activation of the early caspase 8, the signal for Bax-triggered apoptosis is integrated within the cell (43). Other enzymes, including nucleases and protein kinases, may also participate in apoptosis (43). As the signal for Chlamydia-induced apoptosis would presumably originate at the inclusion, it is thus conceivable that this cell death pathway could resemble the pathway set off by Bax or oncogenes.
Besides the proapoptotic activity described here, it has been reported
recently that Chlamydia protects infected cells from
apoptosis due to other ligands, including TNF-, Fas Ab, and granzyme
B/perforin, and that the protection is evident within 4 h of
infection (10). Thus, the antiapoptotic activity may protect infected
cells during the initial stages of chlamydial invasion (10).
Interestingly, the antiapoptotic activity of Chlamydia
infection is due to inhibition of caspase 3 activation (10), which is
required for apoptosis following the TNF- and Fas pathways. As the
proapoptotic activity of Chlamydia is independent of known
caspases, it should not be affected by caspase-3 inactivation. Hence,
there may be a fine balance struck between the anti- and
proapoptotic activities of Chlamydia during the course of
the infection. While antiapoptotic activity may protect infected cells
from lysis by effector cells and cytokines of the host immune system,
proapoptotic activity may contribute to the inflammatory response,
as macrophages and perhaps other cells undergoing apoptosis may secrete
proinflammatory cytokines. The exact contribution from each of these
activities to the pathology of the infection will now need to be
evaluated, although it is conceivable that the antiapoptotic activity
may be operative mainly at the beginning of the infection, with
proapoptotic behavior becoming prevalent at later stages.
|
Acknowledgments |
|---|
|
Footnotes |
|---|
2 Address correspondence and reprint requests to Dr. David Ojcius, Institut Pasteur, Unité de Biologie des Interactions Cellulaires, 25 rue du Dr. Roux, 75724 Paris Cedex 15, France. E-mail address:
3 Abbreviations used in this paper: EB, elementary body; m.o.i., multiplicity of infection; PI, propidium iodide; RB, reticulate body; TUNEL, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling; ICE, IL-1ß-converting enzyme.
Received for publication March 23, 1998. Accepted for publication June 22, 1998.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. A. Paschen, J. G. Christian, J. Vier, F. Schmidt, A. Walch, D. M. Ojcius, and G. Hacker Cytopathicity of Chlamydia is largely reproduced by expression of a single chlamydial protease J. Cell Biol., October 23, 2008; 182(1): 117 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Cheng, P. Shivshankar, Z. Li, L. Chen, I-T. Yeh, and G. Zhong Caspase-1 Contributes to Chlamydia trachomatis-Induced Upper Urogenital Tract Inflammatory Pathologies without Affecting the Course of Infection Infect. Immun., February 1, 2008; 76(2): 515 - 522. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Gong, S. Hay, K. R. Marshall, A. W. Munro, and N. S. Scrutton DNA Binding Suppresses Human AIF-M2 Activity and Provides a Connection between Redox Chemistry, Reactive Oxygen Species, and Apoptosis J. Biol. Chem., October 12, 2007; 282(41): 30331 - 30340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Darville, L. Welter-Stahl, C. Cruz, A. A. Sater, C. W. Andrews Jr., and D. M. Ojcius Effect of the Purinergic Receptor P2X7 on Chlamydia Infection in Cervical Epithelial Cells and Vaginally Infected Mice J. Immunol., September 15, 2007; 179(6): 3707 - 3714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ying, S. F. Fischer, M. Pettengill, D. Conte, S. A. Paschen, D. M. Ojcius, and G. Hacker Characterization of Host Cell Death Induced by Chlamydia trachomatis Infect. Immun., November 1, 2006; 74(11): 6057 - 6066. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Equils, D. Lu, M. Gatter, S. S. Witkin, C. Bertolotto, M. Arditi, J. A. McGregor, C. F. Simmons, and C. J. Hobel Chlamydia Heat Shock Protein 60 Induces Trophoblast Apoptosis through TLR4 J. Immunol., July 15, 2006; 177(2): 1257 - 1263. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R.A. Lyons, E. Saridogan, and O. Djahanbakhch The reproductive significance of human Fallopian tube cilia Hum. Reprod. Update, July 1, 2006; 12(4): 363 - 372. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Desnues, M. Ihrig, D. Raoult, and J.-L. Mege Whipple's Disease: a Macrophage Disease Clin. Vaccine Immunol., February 1, 2006; 13(2): 170 - 178. [Full Text] [PDF]
|
|
|
|
 |
|
 A. Eley, S. Hosseinzadeh, H. Hakimi, I. Geary, and A.A. Pacey Apoptosis of ejaculated human sperm is induced by co-incubation with Chlamydia trachomatis lipopolysaccharide Hum. Reprod., September 1, 2005; 20(9): 2601 - 2607. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yaraei, L. A. Campbell, X. Zhu, W. C. Liles, C.-c. Kuo, and M. E. Rosenfeld Chlamydia pneumoniae Augments the Oxidized Low-Density Lipoprotein-Induced Death of Mouse Macrophages by a Caspase-Independent Pathway Infect. Immun., July 1, 2005; 73(7): 4315 - 4322. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Fischer, T. Harlander, J. Vier, and G. Hacker Protection against CD95-Induced Apoptosis by Chlamydial Infection at a Mitochondrial Step Infect. Immun., February 1, 2004; 72(2): 1107 - 1115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Greene, Y. Xiao, Y. Huang, G. McClarty, and G. Zhong Chlamydia-Infected Cells Continue To Undergo Mitosis and Resist Induction of Apoptosis Infect. Immun., January 1, 2004; 72(1): 451 - 460. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Dockrell, H. M. Marriott, L. R. Prince, V. C. Ridger, P. G. Ince, P. G. Hellewell, and M. K. B. Whyte Alveolar Macrophage Apoptosis Contributes to Pneumococcal Clearance in a Resolving Model of Pulmonary Infection J. Immunol., November 15, 2003; 171(10): 5380 - 5388. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Greub, J.-L. Mege, and D. Raoult Parachlamydia acanthamoeba Enters and Multiplies within Human Macrophages and Induces Their Apoptosis Infect. Immun., October 1, 2003; 71(10): 5979 - 5985. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Jia, M. Alaoui-El-Azher, M. Chow, T. C. Chambers, H. Baker, and S. Jin c-Jun NH2-Terminal Kinase-Mediated Signaling Is Essential for Pseudomonas aeruginosa ExoS-Induced Apoptosis Infect. Immun., June 1, 2003; 71(6): 3361 - 3370. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Perfettini, D. M. Ojcius, C. W. Andrews Jr., S. J. Korsmeyer, R. G. Rank, and T. Darville Role of Proapoptotic BAX in Propagation of Chlamydia muridarum (the Mouse Pneumonitis Strain of Chlamydia trachomatis) and the Host Inflammatory Response J. Biol. Chem., March 7, 2003; 278(11): 9496 - 9502. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Eskra, A. Mathison, and G. Splitter Microarray Analysis of mRNA Levels from RAW264.7 Macrophages Infected with Brucella abortus Infect. Immun., March 1, 2003; 71(3): 1125 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Lu, Z. Xing, and R. C. Brunham GM-CSF Transgene-Based Adjuvant Allows the Establishment of Protective Mucosal Immunity Following Vaccination with Inactivated Chlamydia trachomatis J. Immunol., December 1, 2002; 169(11): 6324 - 6331. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Perfettini, T. Darville, A. Dautry-Varsat, R. G. Rank, and D. M. Ojcius Inhibition of Apoptosis by Gamma Interferon in Cells and Mice Infected with Chlamydia muridarum (the Mouse Pneumonitis Strain of Chlamydia trachomatis) Infect. Immun., May 1, 2002; 70(5): 2559 - 2565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Mueller, R. A. Wilkinson, and J. A. Fishman Listeria monocytogenes Infection in Caspase-11-Deficient Mice Infect. Immun., May 1, 2002; 70(5): 2657 - 2664. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Stenner-Liewen, H. Liewen, J. M. Zapata, K. Pawlowski, A. Godzik, and J. C. Reed CADD, a Chlamydia Protein That Interacts with Death Receptors J. Biol. Chem., March 15, 2002; 277(12): 9633 - 9636. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. ARAKAKI, F. HIGA, M. KOIDE, M. TATEYAMA, and A. SAITO Induction of apoptosis of human macrophages in vitro by Legionella longbeachae through activation of the caspase pathway J. Med. Microbiol., February 1, 2002; 51(2): 159 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Perfettini, J. C. Reed, N. Israel, J.-C. Martinou, A. Dautry-Varsat, and D. M. Ojcius Role of Bcl-2 Family Members in Caspase-Independent Apoptosis during Chlamydia Infection Infect. Immun., January 1, 2002; 70(1): 55 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Rajalingam, H. Al-Younes, A. Muller, T. F. Meyer, A. J. Szczepek, and T. Rudel Epithelial Cells Infected with Chlamydophila pneumoniae (Chlamydia pneumoniae) Are Resistant to Apoptosis Infect. Immun., December 1, 2001; 69(12): 7880 - 7888. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Aoshiba, J. Tamaoki, and A. Nagai Acute cigarette smoke exposure induces apoptosis of alveolar macrophages Am J Physiol Lung Cell Mol Physiol, December 1, 2001; 281(6): L1392 - L1401. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Wahl, F. Oswald, U. Simnacher, S. Weiss, R. Marre, and A. Essig Survival of Chlamydia pneumoniae-Infected Mono Mac 6 Cells Is Dependent on NF-kappa B Binding Activity Infect. Immun., November 1, 2001; 69(11): 7039 - 7045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Fischer, C. Schwarz, J. Vier, and G. Hacker Characterization of Antiapoptotic Activities of Chlamydia pneumoniae in Human Cells Infect. Immun., November 1, 2001; 69(11): 7121 - 7129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Dean and V. C. Powers Persistent Chlamydia trachomatis Infections Resist Apoptotic Stimuli Infect. Immun., April 1, 2001; 69(4): 2442 - 2447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Goth and R. S. Stephens Rapid, Transient Phosphatidylserine Externalization Induced in Host Cells by Infection with Chlamydia spp. Infect. Immun., February 1, 2001; 69(2): 1109 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Coutinho-Silva, J.-L. Perfettini, P. M. Persechini, A. Dautry-Varsat, and D. M. Ojcius Modulation of P2Z/P2X7 receptor activity in macrophages infected with Chlamydia psittaci Am J Physiol Cell Physiol, January 1, 2001; 280(1): C81 - C89. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Jendro, T. Deutsch, B. Korber, L. Kohler, J. G. Kuipers, B. Krausse-Opatz, J. Westermann, E. Raum, and H. Zeidler Infection of Human Monocyte-Derived Macrophages with Chlamydia trachomatis Induces Apoptosis of T Cells: a Potential Mechanism for Persistent Infection Infect. Immun., December 1, 2000; 68(12): 6704 - 6711. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fettucciari, E. Rosati, L. Scaringi, P. Cornacchione, G. Migliorati, R. Sabatini, I. Fetriconi, R. Rossi, and P. Marconi Group B Streptococcus Induces Apoptosis in Macrophages J. Immunol., October 1, 2000; 165(7): 3923 - 3933. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Behnia, K. A. Robertson, and W. J. Martin II Lung Infections : Role of Apoptosis in Host Defense and Pathogenesis of Disease Chest, June 1, 2000; 117(6): 1771 - 1777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-L. Perfettini, T. Darville, G. Gachelin, P. Souque, M. Huerre, A. Dautry-Varsat, and D. M. Ojcius Effect of Chlamydia trachomatis Infection and Subsequent Tumor Necrosis Factor Alpha Secretion on Apoptosis in the Murine Genital Tract Infect. Immun., April 1, 2000; 68(4): 2237 - 2244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Coutinho-Silva, P. M. Persechini, R. D. C. Bisaggio, J.-L. Perfettini, A. C. T. D. S. Neto, J. M. Kanellopoulos, I. Motta-Ly, A. Dautry-Varsat, and D. M. Ojcius P2Z/P2X7 receptor-dependent apoptosis of dendritic cells Am J Physiol Cell Physiol, May 1, 1999; 276(5): C1139 - C1147. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
