The release of damage-associated molecular patterns, including uridine triphosphate (UTP) and adenosine triphosphate (ATP) to the extracellular milieu is a key component of innate immune response to infection. Previously, we showed that macrophage infection by the protozoan parasite Leishmania amazonensis—the etiological agent of cutaneous leishmaniasis—can be controlled by ATP- and UTP-mediated activation of P2Y and P2X7 receptors (activated by UTP/ATP and ATP, respectively), which provided comparable immune responses against the parasite. Interestingly, in context of Leishmania amazonensis infection, UTP/P2Y triggered apoptosis, reactive oxygen species, and oxide nitric (NO) production, which are characteristic of P2X7 receptor activation. Here, we examined a possible “cross-talk” between P2Y2 and P2X7 receptors, and the requirement for pannexin-1 (PANX-1) in the control of L. amazonensis infection in mouse peritoneal macrophages and in vivo. UTP treatment reduced L. amazonensis parasite load, induced extracellular ATP release [which was pannexin-1 (PANX-1) dependent], and triggered leukotriene B4 (LTB4) production in macrophages. UTP-induced parasite control was blocked by pharmacological antagonism of P2Y2 or P2X7 receptors and was absent in macrophages lacking P2X7 or PANX-1. In addition, ATP release induced by UTP was also inhibited by PANX-1 blocker carbenoxolone, and partially reversed by inhibitors of vesicle traffic and actin cytoskeleton dynamics. In vivo, UTP treatment reduced footpad and popliteal lymph node parasite load, and the lesion in wild-type (WT) mice; fact not observed in P2X7−/− mice. Our data reveal that P2Y2 and P2X7 receptors cooperate to trigger potent innate immune responses against L. amazonensis infection.
Introduction:Malaria is an infectious-parasitic disease caused by a protozoa of the genus Plasmodium, and is one of the main public health problems worldwide. The parasitosis may progress to severe forms with pulmonary complications associated with acute respiratory distress syndrome (MA-ARDS). Infection with P. falciparum, P. vivax, P. ovale or P. knowlesi can lead to severe respiratory symptoms of MA-ARDS in humans. In murine models of malaria, MA-SDRA is characterized by increased permeability of the pulmonary microvasculature endothelium and inflammation. However, little is known about the immunoregulatory mechanisms associated with the pathogenesis of MA-ARDS.Objective: The aim of this study was to investigate the kinetics of lung innate immune cell recruitment and the polarization profile of alveolar macrophages. C57BL/6 and Balb/c mice were infected with 1x10 6 erythrocytes parasitized with Plasmodium berghei ANKA. Methodology:On days 4 and 6 after infection, the animals were euthanized and the bronchoalveolar lavage (BAL) and tissue digestion was performed to obtain the samples and analyzes. Subpopulations of myeloid cells (inflammatory monocytes, alveolar macrophages, neutrophils and /or eosinophils) present in BAL and lung tissue were analyzed by flow cytometry and nitric oxide, arginase and cytokines were measured in the BAL supernatant.Results: C57BL/6 infected-mice showed pulmonary dysfunction and edema as attested by increased organ weight and protein content in the BAL and pulmonary interstitium. In contrast, BALB/c mice showed a small increase in the organ weight and total proteins in the BAL, alterations that did not interfere with lung function. We observed differences in the percentage and/or total number of inflammatory monocytes and neutrophils, in both compartments, in BALB/c and C57BL/6 mice, throughout the infection. Parasitized mice of both strains, although exhibiting different kinetics, showed reduction in the percentage and total number of alveolar macrophages, throughout the disease. Interestingly, alveolar macrophages of C57BL/6 mice exhibited higher expression of CD206 and MHC class II as well as reduction in the percentage of positive cells for iNOS enzyme. In addition, an increase in arginase and nitric oxide enzyme activities was detected in the BAL of infected C57BL/6 mice. No alteration of eosinophil population was noted throughout the infection in both mouse strains. Analysis of the cytokine profile revealed a significant increase in the ratio between the levels of IFN-γ / IL-10 and TNF-a / IL-10 in the BAL of C57BL/6 infected-mice. Conclusion:Our findings show that C57BL/6 and BALB/c mice exhibit different dynamics of cell population in the lung and plasticity of alveolar macrophages in the BAL, phenomena that may be associated with the development or not of the pulmonary complications observed in C57BL/6 and BALB/c, respectively. This study brings findings about innate immunity cells in development of pulmonary malaria and contributes to the future development of more effect...
O jogo didático, em uma perspectiva de educação crítica, deve compor uma metodologia de ensino que permita ao aluno ser capaz de compreender os conceitos científicos e, ao mesmo tempo, desenvolver suas diferentes habilidades como a cognição, socialização, motivação e criatividade. Partindo deste pressuposto, foi elaborado um jogo que explora questões relacionadas aos contextos sociais e políticos próximos às realidades culturais de alunos de uma escola pública de modo a suscitar reflexões integradas e críticas no ensino de ciências. Este artigo apresenta um relato sobre o contexto de aplicação do jogo "Repensando a cidade" objetivando a discussão de temas socioambientais e políticos sob a perspectiva do enfoque Ciência, Tecnologia e Sociedade (CTS) de modo a contribuir tanto na formação reflexiva dos estudantes como na prática docente de bolsistas do Programa Institucional de Bolsa de Iniciação à Docência (PIBID/CAPES). Os temas abordados no jogo (dinâmica ecológica, poluição, planejamento urbano, saúde, degradação ambiental e reflorestamento) permitiram aos alunos refletirem sobre questões socioambientais diretamente relacionadas às consequências da presença ou ausência de determinadas tecnologias de modo a mobilizarem conhecimentos de diversas naturezas desmistificando, assim, visões naturalizadas e pouco críticas sobre Ciência e Tecnologia.
O jogo didático, dentro de uma perspectiva de educação crítica, deve compor uma metodologia de ensino que permita ao aluno ser capaz de compreender os conceitos científicos e, ao mesmo tempo, desenvolver suas diferentes habilidades como a cognição, socialização, motivação e criatividade. Partindo deste pressuposto, foi elaborado um jogo que explora questões relacionadas aos contextos sociais e políticos próximos às realidades culturais de alunos de uma escola pública de modo a suscitar reflexões integradas e críticas relacionadas ao ensino de ciências. Este artigo apresenta um relato sobre o contexto de aplicação do jogo “Repensando a cidade” objetivando a discussão de assuntos relacionados a temas socioambientais e políticos sob a perspectiva do enfoque Ciência, Tecnologia e Sociedade (CTS) de modo a contribuir tanto na formação reflexiva dos estudantes como na prática docente dos bolsistas do Programa Institucional de Bolsa de Iniciação à Docência (PIBID/CAPES). Os temas abordados no jogo (dinâmica ecológica, poluição, planejamento urbano, saúde, degradação ambiental e reflorestamento) permitiram aos alunos refletirem sobre questões socioambientais diretamente relacionadas às consequências da presença ou ausência de determinadas tecnologias de modo a mobilizarem conhecimentos de diversas naturezas desmistificando, assim, visões naturalizadas e pouco críticas sobre Ciência e Tecnologia.
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