Immunological pathways triggered by porphyromonas gingivalis and fusobacterium nucleatum: Therapeutic possibilities?

Porphyromonas gingivalis (P. gingivalis) and Fusobacterium nucleatum (F. nucleatum) are Gram-negative anaerobic bacteria possessing several virulence factors that make them potential pathogens associated with periodontal disease. Periodontal diseases are chronic inflammatory diseases of the oral cavity, including gingivitis and periodontitis. Periodontitis can lead to tooth loss and is considered one of the most prevalent diseases worldwide. P. gingivalis and F. nucleatum possess virulence factors that allow them to survive in hostile environments by selectively modulating the host\u27s immune-inflammatory response, thereby creating major challenges to host cell survival. Studies have demonstrated that bacterial infection and the host immune responses are involved in the induction of periodontitis. The NLRP3 inflammasome and its effector molecules (IL-1β and caspase-1) play roles in the development of periodontitis. We and others have reported that the purinergic P2X7 receptor plays a role in the modulation of periodontal disease and intracellular pathogen control. Caspase-4/5 (in humans) and caspase-11 (in mice) are important effectors for combating bacterial pathogens via mediation of cell death and IL-1β release. The exact molecular events of the host\u27s response to these bacteria are not fully understood. Here, we review innate and adaptive immune responses induced by P. gingivalis and F. nucleatum infections and discuss the possibility of manipulations of the immune response as therapeutic strategies. Given the global burden of periodontitis, it is important to develop therapeutic targets for the prophylaxis of periodontopathogen infections

Differential involvement of the canonical and noncanonical inflammasomes in the immune response against infection by the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum

We examined the involvement of the P2 × 7 receptor and the canonical and noncanonical inflammasomes in the control of single-species or dual-species infection by the periodontal bacteria Porphyromonas gingivalis and Fusobacterium nucleatum in cells and mice. Stimulation of the P2 × 7 receptor leads to activation of the canonical NLRP3 inflammasome and activation of caspase-1, which leads to cleavage of pro-IL-1β to IL-1β, a key cytokine in the host inflammatory response in periodontal disease. The non-canonical inflammasome pathway involves caspase-11. Thus, wildtype (WT), P2 × 7−/−, caspase-11−/− and caspase-1/11−/− mice were co-infected with both bacterial species. In parallel, bone marrow-derived macrophages (BMDMs) from WT mice and the different knockout mice were infected with P. gingivalis and/or F. nucleatum, and treated or not with extracellular ATP, which is recognized by P2 × 7. F. nucleatum infection alone promoted secretion of IL-1β in BMDMs. Conversely, the canonical pathway involving P2 × 7 and caspase-1 was necessary for secretion of IL-1β in BMDMs infected with P. gingivalis and in the mandible of mice coinfected with P. gingivalis and F. nucleatum. The P2 × 7 pathway can limit bacterial load in single-species and dual-species infection with P. gingivalis and F. nucleatum in BMDMs and in mice. The non-canonical pathway involving caspase-11 was required for secretion of IL-1β induced by F. nucleatum infection in BMDMs, without treatment with ATP. Caspase-11 was also required for induction of cell death during infection with F. nucleatum and contributed to limiting bacterial load during F. nucleatum infection in BMDMs and in the gingival tissue of mice coinfected with P. gingivalis and F. nucleatum. Together, these data suggest that the P2 × 7-caspase-1 and caspase-11 pathways are involved in the immune response against infection by P. gingivalis and F. nucleatum, respectively

Uma viagem pelo sistema digestório : uma proposta de análise do uso de oficina como recurso didático-pedagógico para alunos do ensino superior

O ensino do corpo humano, incluindo-se o sistema digestório, constitui tópico fundamental do ensino de ciências. Apesar de sua importância, o conhecimento de estudantes sobre o tema muitas vezes se apresenta permeado por conceitos em desacordo com a literatura científica contemporânea, incompletos ou mesmo incorretos. A presente proposta pretende analisar o uso da oficina interativa "Uma Viagem pelo Sistema Digestório", como recurso didático-pedagógico para complementar a negociação de significados, e a reconstrução de conceitos sobre fisiologia digestória humana em estudantes do ensino superior. Visamos promover a ampliação conceitual sobre a temática valendose da incorporação dos saberes científicos vigentes aos conhecimentos prévios trazidos pelos discentes, facilitando, assim, o desenvolvimento cognitivo do aluno

The P2X7 receptor mediates Toxoplasma gondii Control in Macrophages through canonical NLRP3 inflammasome activation and reactive oxygen species production

Toxoplasma gondii (T. gondii) is the protozoan parasite that causes toxoplasmosis, a potentially fatal disease to immunocompromised patients, and which affects approximately 30% of the world\u27s population. Previously, we showed that purinergic signaling via the P2X7 receptor contributes to T. gondii elimination in macrophages, through reactive oxygen species (ROS) production and lysosome fusion with the parasitophorous vacuole. Moreover, we demonstrated that P2X7 receptor activation promotes the production of anti-parasitic pro-inflammatory cytokines during early T. gondii infection in vivo. However, the cascade of signaling events that leads to parasite elimination via P2X7 receptor activation remained to be elucidated. Here, we investigated the cellular pathways involved in T. gondii elimination triggered by P2X7 receptor signaling, during early infection in macrophages. We focused on the potential role of the inflammasome, a protein complex that can be co-activated by the P2X7 receptor, and which is involved in the host immune defense against T. gondii infection. Using peritoneal and bone marrow-derived macrophages from knockout mice deficient for inflammasome components (NLRP3-/-, Caspase-1/11-/-, Caspase-11-/-), we show that the control of T. gondii infection via P2X7 receptor activation by extracellular ATP (eATP) depends on the canonical inflammasome effector caspase-1, but not on caspase-11 (a non-canonical inflammasome effector). Parasite elimination via P2X7 receptor and inflammasome activation was also dependent on ROS generation and pannexin-1 channel. Treatment with eATP increased IL-1β secretion from infected macrophages, and this effect was dependent on the canonical NLRP3 inflammasome. Finally, treatment with recombinant IL-1β promoted parasite elimination via mitochondrial ROS generation (as assessed using Mito-TEMPO). Together, our results support a model where P2X7 receptor activation by eATP inhibits T. gondii growth in macrophages by triggering NADPH-oxidase-dependent ROS production, and also by activating a canonical NLRP3 inflammasome, which increases IL-1β production (via caspase-1 activity), leading to mitochondrial ROS generation

Purinergic signaling in the modulation of redox biology

Purinergic signaling is a cell communication pathway mediated by extracellular nucleotides and nucleosides. Tri- and diphosphonucleotides are released in physiological and pathological circumstances activating purinergic type 2 receptors (P2 receptors): P2X ion channels and P2Y G protein-coupled receptors. The activation of these receptors triggers the production of reactive oxygen and nitrogen species and alters antioxidant defenses, modulating the redox biology of cells. The activation of P2 receptors is controlled by ecto-enzymes named ectonucleotidases, E-NTPDase1/CD39 and ecto-5’-nucleotidase/CD73) being the most relevant. The first enzyme hydrolyzes adenosine triphosphate (ATP) and adenosine diphosphate (ADP) into adenosine monophosphate (AMP), and the second catalyzes the hydrolysis of AMP to adenosine. The activity of these enzymes is diminished by oxidative stress. Adenosine actives P1 G-coupled receptors that, in general, promote the maintenance of redox hemostasis by decreasing reactive oxygen species (ROS) production and increase antioxidant enzymes. Intracellular purine metabolism can also contribute to ROS generation via xanthine oxidase activity, which converts hypoxanthine into xanthine, and finally, uric acid. In this review, we describe the mechanisms of redox biology modulated by purinergic signaling and how this signaling may be affected by disturbances in the redox homeostasis of cells

The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?

Under physiological conditions, adenosine triphosphate (ATP) is present at low levels in the extracellular milieu, being massively released by stressed or dying cells. Once outside the cells, ATP and related nucleotides/nucleoside generated by ectonucleotidases mediate a high evolutionary conserved signaling system: the purinergic signaling, which is involved in a variety of pathological conditions, including inflammatory diseases. Extracellular ATP has been considered an endogenous adjuvant that can initiate inflammation by acting as a danger signal through the activation of purinergic type 2 receptors—P2 receptors (P2Y G-protein coupled receptors and P2X ligand-gated ion channels). Among the P2 receptors, the P2X7 receptor is the most extensively studied from an immunological perspective, being involved in both innate and adaptive immune responses. P2X7 receptor activation induces large-scale ATP release via its intrinsic ability to form a membrane pore or in association with pannexin hemichannels, boosting purinergic signaling. ATP acting via P2X7 receptor is the second signal to the inflammasome activation, inducing both maturation and release of pro-inflammatory cytokines, such as IL-1β and IL-18, and the production of reactive nitrogen and oxygen species. Furthermore, the P2X7 receptor is involved in caspases activation, as well as in apoptosis induction. During adaptive immune response, P2X7 receptor modulates the balance between the generation of T helper type 17 (Th17) and T regulatory (Treg) lymphocytes. Therefore, this receptor is involved in several inflammatory pathological conditions. In infectious diseases and cancer, P2X7 receptor can have different and contrasting effects, being an angel or a demon depending on its level of activation, cell studied, type of pathogen, and severity of infection. In neuroinflammatory and neurodegenerative diseases, P2X7 upregulation and function appears to contribute to disease progression. In this review, we deeply discuss P2X7 receptor dual function and its pharmacological modulation in the context of different pathologies, and we also highlight the P2X7 receptor as a potential target to treat inflammatory related diseases

Interação museu-escola : a importância dos programas de formação continuada de professores em municípios afastados dos centros urbanos

Due to a series of misconceptions about science, science centers and science museums have proposed projects to break the paradigm of science education focused on a small portion of the population. These centers and museums have developed strategies aimed at social inclusion in terms of their educational character, thereby investing in strategies to upgrade vocational education, among other actions. However, most of these areas are concentrated in large urban areas, preventing the participation of the poorest sectors of society. Thus, this study shows a report of a pilot teacher education program developed by the Espaço Ciência InterAtiva do IFRJ, a science museum located in a suburban area of Rio de Janeiro, showing that a scientific exhibition can contribute to the inclusion of teachers in these areas of informal education, and to their ongoing training.En raison d’un ensemble de conceptions erronées sur la science, les centres et les musées des sciences se proposent actuellement de rompre avec l’image de la science réservée à une petite partie de la population. Ces espaces développent des activités qui, par leur caractère éducatif, favorisent l’intégration sociale, et investissent de cette façon, entre autres actions, dans des stratégies de mise à niveau des professionnels de l’éducation. Toutefois, la plupart de ces espaces se concentrent dans les grands centres urbains, ce qui rend la participation des couches moins favorisées de la société bien plus difficile. Ainsi, ce travail porte sur l’exposé d’un programme pilote de formation continue des enseignants, développé par l’Espaço Ciência InterAtiva (Espace Science Interactive) de l’IFRJ1 - un musée des sciences situé dans une région périphérique de Rio de Janeiro, et démontre qu’une exposition scientifique peut contribuer à l’insertion d’enseignants dans ces espaces d’éducation non formelle ainsi qu’à leur formation continue.En virtud de una serie de conceptos equivocados respecto a la ciencia, los centros y museos de ciencias surgen con propuestas para romper con el paradigma de la ciencia accesible solo a una pequeña parte de la población. Estos espacios desarrollan actividades con fines de inclusión social en función de su carácter educativo, y así invierten, entre otras acciones, en estrategias para la actualización de los profesionales de la educación. La mayor parte de estos espacios se concentran aún en los grandes centros urbanos, dificultando la participación de las clases sociales menos favorecidas. Este trabajo presenta un programa piloto de formación continua de profesores desarrollado por el Espaço Ciência InterAtiva del IFRJ (Instituto Federal de Río de Janeiro), un museo de ciencias ubicado en una región periférica de Rio de Janeiro, demostrando así que una exposición científica puede contribuir a la inserción de los docentes en los espacios de educación no formal, así como a la formación continua de los mismos.Em virtude de uma série de concepções equivocadas a respeito da ciência, os centros e museus de ciências surgem com propostas de romper com o paradigma da ciência voltada para uma pequena parcela da população. Esses espaços desenvolvem atividades com vistas à inclusão social em função do seu caráter educacional, e com isso investem, entre outras ações, em estratégias de atualização do profissional da educação. Todavia, a maior parte desses espaços concentra-se nos grandes centros urbanos, dificultando a participação das camadas menos favorecidas da sociedade. Dessa forma, o presente trabalho apresenta o relato de um programa piloto de formação continuada de professores, desenvolvido pelo Espaço Ciência InterAtiva do IFRJ, um museu de ciências localizado em uma região periférica do Rio de Janeiro, demonstrando assim que uma exposição científica pode contribuir para a inserção dos docentes nesses espaço de educação não formal, bem como para a formação continuada dos mesmos

Interação museu-escola : a importância dos programas de formação continuada de professores em municípios afastados dos centros urbanos

Due to a series of misconceptions about science, science centers and science museums have proposed projects to break the paradigm of science education focused on a small portion of the population. These centers and museums have developed strategies aimed at social inclusion in terms of their educational character, thereby investing in strategies to upgrade vocational education, among other actions. However, most of these areas are concentrated in large urban areas, preventing the participation of the poorest sectors of society. Thus, this study shows a report of a pilot teacher education program developed by the Espaço Ciência InterAtiva do IFRJ, a science museum located in a suburban area of Rio de Janeiro, showing that a scientific exhibition can contribute to the inclusion of teachers in these areas of informal education, and to their ongoing training.En raison d’un ensemble de conceptions erronées sur la science, les centres et les musées des sciences se proposent actuellement de rompre avec l’image de la science réservée à une petite partie de la population. Ces espaces développent des activités qui, par leur caractère éducatif, favorisent l’intégration sociale, et investissent de cette façon, entre autres actions, dans des stratégies de mise à niveau des professionnels de l’éducation. Toutefois, la plupart de ces espaces se concentrent dans les grands centres urbains, ce qui rend la participation des couches moins favorisées de la société bien plus difficile. Ainsi, ce travail porte sur l’exposé d’un programme pilote de formation continue des enseignants, développé par l’Espaço Ciência InterAtiva (Espace Science Interactive) de l’IFRJ1 - un musée des sciences situé dans une région périphérique de Rio de Janeiro, et démontre qu’une exposition scientifique peut contribuer à l’insertion d’enseignants dans ces espaces d’éducation non formelle ainsi qu’à leur formation continue.En virtud de una serie de conceptos equivocados respecto a la ciencia, los centros y museos de ciencias surgen con propuestas para romper con el paradigma de la ciencia accesible solo a una pequeña parte de la población. Estos espacios desarrollan actividades con fines de inclusión social en función de su carácter educativo, y así invierten, entre otras acciones, en estrategias para la actualización de los profesionales de la educación. La mayor parte de estos espacios se concentran aún en los grandes centros urbanos, dificultando la participación de las clases sociales menos favorecidas. Este trabajo presenta un programa piloto de formación continua de profesores desarrollado por el Espaço Ciência InterAtiva del IFRJ (Instituto Federal de Río de Janeiro), un museo de ciencias ubicado en una región periférica de Rio de Janeiro, demostrando así que una exposición científica puede contribuir a la inserción de los docentes en los espacios de educación no formal, así como a la formación continua de los mismos.Em virtude de uma série de concepções equivocadas a respeito da ciência, os centros e museus de ciências surgem com propostas de romper com o paradigma da ciência voltada para uma pequena parcela da população. Esses espaços desenvolvem atividades com vistas à inclusão social em função do seu caráter educacional, e com isso investem, entre outras ações, em estratégias de atualização do profissional da educação. Todavia, a maior parte desses espaços concentra-se nos grandes centros urbanos, dificultando a participação das camadas menos favorecidas da sociedade. Dessa forma, o presente trabalho apresenta o relato de um programa piloto de formação continuada de professores, desenvolvido pelo Espaço Ciência InterAtiva do IFRJ, um museu de ciências localizado em uma região periférica do Rio de Janeiro, demonstrando assim que uma exposição científica pode contribuir para a inserção dos docentes nesses espaço de educação não formal, bem como para a formação continuada dos mesmos