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Originally published online as doi:10.1189/jlb.1001877 on April 1, 2004

Published online before print April 1, 2004
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(Journal of Leukocyte Biology. 2004;76:95-103.)
© 2004 by Society for Leukocyte Biology

Leishmania major-mediated prevention of programmed cell death induction in infected macrophages is associated with the repression of mitochondrial release of cytochrome c

Khadija Akarid*,{dagger},1, Damien Arnoult*, Juliette Micic-Polianski*, Jamila Sif{dagger}, Jérôme Estaquier* and Jean Claude Ameisen*,2

* EMIU9922, INSERM/Université Paris 7, IFR02, APHP, Faculté de Médecine Xavier Bichat, France; and
{dagger} Département de Biologie, Faculté des Sciences, El Jadida, Morocco

2Correspondence: EMI-U 9922, INSERM/Université Paris 7, Faculté de Médecine Xavier Bichat, 16, Rue Henri Huchard, 75870 Paris Cedex 18, France. E-mail: ameisen{at}wanadoo.fr

Leishmania are obligate, intracellular parasites of macrophages in their vertebrate hosts, including humans, in which they cause disease. Here, we report that in vitro infection with Leishmania major protects murine bone marrow-derived macrophages against programmed cell death (PCD) induced by deprival of macrophage-colony stimulating factor and delays PCD caused by treatment with staurosporine, a broad inducer of PCD. This preventive effect was observed in macrophages from L. major-susceptible BALB/c and L. major-resistant C57BL/6 mice, indicating that repression of PCD did not depend on genetic background-specific regulation of T helper cell type 1 (Th1)/Th2 cytokine secretion. Prevention of effector caspase activation and PCD was associated with a repression of mitochondrial release of cytochrome c and did not involve the nuclear factor-{kappa}B pathway. The capacity of L. major to delay PCD induction in the infected macrophages may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.

Key Words: apoptosis • mononuclear phagocyte • intracellular parasite • mitochondria • caspase activation




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