Leishmania major-mediated prevention of programmed cell death induction in infected macrophages is associated with the repression of mitochondrial release of cytochrome c.
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-kappaB 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.
Akarid
Khadija
K
INSERM/Université Paris 7, Faculté de Médecine Xavier Bichat, 16, Rue Henri Huchard, 75870 Paris Cedex 18, France.
Arnoult
Damien
D
Micic-Polianski
Juliette
J
Sif
Jamila
J
Estaquier
Jérôme
J
Ameisen
Jean Claude
JC
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism*; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007150:Immunohistochemistry; D018320:Leishmania major / Q000276:immunology; D007896:Leishmaniasis / Q000276:immunology*; D008264:Macrophages / Q000469:parasitology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000469:parasitology*; D019311:Staurosporine / Q000494:pharmacology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D004791:Enzyme Inhibitors; D045304:Cytochromes c; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D019311:Staurosporine