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Published online before print April 1, 2004

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1001877

Received for publication October 10, 2001.
Revised January 27, 2004.
Accepted for publication February 4, 2004.

Article

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 ^*, Damien Arnoult ^*, Juliette Micic-Polianski ^*, Jamila Sif , Jérôme Estaquier ^*, and Jean Claude Ameisen ^*@

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

^@ To whom correspondence should be addressed. E-mail: ameisen{at}wanadoo.fr.

	Abstract

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-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