Leishmania mexicana: inhibition of camptothecin-induced apoptosis of monocyte-derived dendritic cells.
Macrophages (Mphi) and dendritic cells (DC) are the major target cell populations of the obligate intracellular parasite Leishmania. Inhibition of host cell apoptosis is a method employed by multiple pathogens to ensure their survival in the infected cell. Leishmania has been shown to protect Mphi and neutrophils from both natural and induced apoptosis. As shown in this study, apoptosis in monocyte-derived dendritic cells (moDC) induced by treatment with camptothecin was downregulated by coincubation with L. mexicana, as detected by morphological analysis of cell nuclei, TUNEL assay, gel electrophoresis of low molecular weight DNA fragments, and annexin V binding to phosphatidylserine. The observed antiapoptotic effect was found to be associated with a significant reduction of caspase-3 activity in moDC. The capacity of L. mexicana to delay apoptosis induction in the infected moDC may have implications for Leishmania pathogenesis by favoring the invasion of its host and the persistence of the parasite in the infected cells.
Valdés-Reyes
Leonardo
L
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Dr. Balmis 148, Col. Doctores, México, D.F. 06726, Mexico.
Argueta
Jesús
J
Morán
Julio
J
Salaiza
Norma
N
Hernández
Joselín
J
Berzunza
Miriam
M
Aguirre-García
Magdalena
M
Becker
Ingeborg
I
Gutiérrez-Kobeh
Laila
L
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001399:Azure Stains; D002166:Camptothecin / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D053938:DNA Fragmentation; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000469:parasitology*; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007894:Leishmania mexicana / Q000502:physiology*; D009000:Monocytes / Q000166:cytology
D000972:Antineoplastic Agents, Phytogenic; D001399:Azure Stains; D053148:Caspase 3; D002166:Camptothecin