Leishmania mexicana amastigotes inhibit p38 and JNK and activate PI3K/AKT: role in the inhibition of apoptosis of dendritic cells.
Leishmania mexicana is the causal agent of cutaneous leishmaniasis in Mexico. Dendritic cells (DC) are one of the host cells of Leishmania parasites. Intracellular microorganisms inhibit host cell apoptosis as a strategy to ensure their survival in infected cells. We have previously shown that Leishmania mexicana promastigotes and amastigotes inhibit camptothecin-induced apoptosis of monocyte-derived dendritic cells (moDC), but the mechanisms underlying the inhibition of apoptosis of DC by Leishmania have not been established. MAP kinases and PI3K participate in the process of apoptosis and are modulated by different species of Leishmania. As shown in this study, the infection of moDC with L. mexicana amastigotes diminished significantly the phosphorylation of the MAP kinases p38 and JNK. The inhibition of both kinases diminished significantly DNA fragmentation in moDC stimulated with camptothecin. On the other hand, L. mexicana amastigotes were able to activate the anti-apoptotic pathways PI3K and AKT. Our results indicate that L. mexicana amastigotes have the capacity to diminish MAP kinases activation and activate PI3K and AKT, which is probably one of the strategies employed by L. mexicana amastigotes to inhibit apoptosis in the infected moDC.
Laboratorio de Microbiología y Parasitología, Facultad de Ciencias de la Salud, Av. Universidad Anáhuac Norte, Lomas Anáhuac, Huixquilucan, México.
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R
Vázquez-López
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.
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Argueta-Donohué
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.
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Wilkins-Rodríguez
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.
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A
Escalona-Montaño
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.
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M
Aguirre-García
Unidad de Investigación en Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, México, D. F. México.
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Gutiérrez-Kobeh
D000328:Adult; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000469:parasitology / Q000473:pathology; D006801:Humans; D007894:Leishmania mexicana / Q000254:growth & development / Q000276:immunology*; D007896:Leishmaniasis / Q000276:immunology* / Q000469:parasitology*; D008297:Male; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D055815:Young Adult; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D019869:Phosphatidylinositol 3-Kinases; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases; D002166:Camptothecin
Leishmania mexicana; PI3K; amastigotes; apoptosis; dendritic cells; mitogen-activated protein kinase