Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/9467
Title: Cooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis.
Authors: Wanderley, João Luiz Mendes
Silva, Lucia Helena Pinto da
Deolindo, Poliana
Soong, Lynn
Borges, Valeria de Matos
Prates, Deboraci Brito
Souza, Ana Paula Almeida de
Barral, Aldina Maria Prado
Balanco, José Mario de Freitas
Nascimento, Michelle Tanny Cunha do
Saraiva, Elvira Maria B
Barcinski, Marcello André
Affilliation: National Cancer Institute. Experimental Medicine Division. Rio de Janeiro, RJ, Brasil / Federal University of Rio de Janeiro. Biomedical Sciences Institute. Morphological Sciences Program. Rio de Janeiro, RJ, Brasil
National Cancer Institute. Experimental Medicine Division. Rio de Janeiro, RJ, Brasil / Federal Rural University of Rio de Janeiro. Veterinary Institute. Department of Microbiology and Veterinary Immunology. Rio de Janeiro, RJ, Brasil
National Cancer Institute. Experimental Medicine Division. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Molecular and Cellular Biology Program. Rio de Janeiro, RJ, Brasil
University of Texas Medical Branch. Center for Biodefense and Emerging Infectious Diseases, Sealy Center for Vaccine Development. Departments of Microbiology and Immunology and of Pathology. Galveston, Texas, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of Sao Paulo. Parasitology Department. Biomedical Sciences Institute. Sao Paulo, SP, Brasil
Federal University of Rio de Janeiro. Microbiology Institute. Immunology Department. Rio de Janeiro, RJ, Brasil
Federal University of Rio de Janeiro. Microbiology Institute. Immunology Department. Rio de Janeiro, RJ, Brasil
National Cancer Institute. Experimental Medicine Division. Rio de Janeiro, RJ, Brasil / University of Sao Paulo. Parasitology Department. Biomedical Sciences Institute. Sao Paulo, SP, Brasil
Abstract: Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a subpopulation of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen.
DeCS: Apoptose
Leishmania mexicana/citologia
Leishmania mexicana/crescimento & desenvolvimento
Leishmaniose/patologia
Leishmaniose/parasitologia
Estágios do Ciclo de Vida
Animais
Sistema Digestório/citologia
Marcação In Situ das Extremidades Cortadas
Leishmania mexicana/patogenicidade
Camundongos
Fosfatidilserinas/metabolismo
Psychodidae/citologia
Psychodidae/parasitologia
Issue Date: 2009
Publisher: Public Library of Science
Citation: WANDERLEY, J. L. M. et al. Cooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis. PLoS One, v. 4, n. 5, p. e5733, 2009.
DOI: 10.1371/journal.pone.0005733
ISSN: 1932-6203
Copyright: open access
Appears in Collections:BA - IGM - Artigos de Periódicos

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