Cooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis.

dc.creatorWanderley, João Luiz Mendes
dc.creatorSilva, Lucia Helena Pinto da
dc.creatorDeolindo, Poliana
dc.creatorSoong, Lynn
dc.creatorBorges, Valeria de Matos
dc.creatorPrates, Deboraci Brito
dc.creatorSouza, Ana Paula Almeida de
dc.creatorBarral, Aldina Maria Prado
dc.creatorBalanco, José Mario de Freitas
dc.creatorNascimento, Michelle Tanny Cunha do
dc.creatorSaraiva, Elvira Maria B
dc.creatorBarcinski, Marcello André
dc.date2015-02-09T18:43:44Z
dc.date2015-02-09T18:43:44Z
dc.date2009
dc.date.accessioned2023-09-26T23:17:53Z
dc.date.available2023-09-26T23:17:53Z
dc.identifierWANDERLEY, 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.
dc.identifier1932-6203
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/9467
dc.identifier10.1371/journal.pone.0005733
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8889011
dc.descriptionMimicking 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.subjectApoptose
dc.subjectLeishmania mexicana/citologia
dc.subjectLeishmania mexicana/crescimento & desenvolvimento
dc.subjectLeishmaniose/patologia
dc.subjectLeishmaniose/parasitologia
dc.subjectEstágios do Ciclo de Vida
dc.subjectAnimais
dc.subjectSistema Digestório/citologia
dc.subjectMarcação In Situ das Extremidades Cortadas
dc.subjectLeishmania mexicana/patogenicidade
dc.subjectCamundongos
dc.subjectFosfatidilserinas/metabolismo
dc.subjectPsychodidae/citologia
dc.subjectPsychodidae/parasitologia
dc.titleCooperation between apoptotic and viable metacyclics enhances the pathogenesis of Leishmaniasis.
dc.typeArticle


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