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-Induced Apoptosis and Microbicidal Activity in Monocytes Harboring the Intracellular Bacterium Coxiella burnetii Require Membrane TNF and Homotypic Cell Adherence1
Unité des Rickettsies, Unité Mixte de Recherche 6020, Centre National de la Recherche Scientifique, Faculté de Médecine, Université de la Méditerranée, Marseille, France
IFN-
is critical for the protection against intracellular
bacteria through activation of the antimicrobial machinery of
phagocytes. Coxiella burnetii, the etiological agent of
Q fever, is a strictly intracellular bacterium that inhabits
monocytes/macrophages. We previously showed that IFN-
induced
C. burnetii killing by promoting the apoptosis of
infected monocytes. We show in this study that IFN-
-induced
apoptosis of infected monocytes was characterized by a time- and
dose-dependent activation of caspase-3. IFN-
-mediated caspase-3
activation and C. burnetii killing depend on the
expression of membrane TNF. Indeed, TNF was transiently
expressed on the cell surface of infected monocytes a few hours after
IFN-
treatment. In addition, anti-TNF Abs inhibited
IFN-
-mediated caspase-3 activation whereas soluble TNF had no effect
on infected cells. Concomitantly, IFN-
induced homotypic adherence
of C. burnetii-infected monocytes. The latter required
the interaction of
2 integrins with CD54. When adherence
was disrupted by pipetting, by a combination of Abs specific for CD11b,
CD18, and CD54, or by an antisense oligonucleotide targeting CD18 mRNA,
both cell apoptosis and bacterial killing induced by IFN-
were
inhibited. Thus, adherence via CD54/
2 integrins together
with membrane TNF are required to eliminate C.
burnetii-infected cells through cell contact-dependent
apoptosis. Our results reveal a new component of the antimicrobial
arsenal mobilized by IFN-
against infection by intracellular
bacteria.
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