Vaccination with Leishmania infantum Acidic Ribosomal P0 but Not with Nucleosomal Histones Proteins Controls Leishmania infantum Infection in Hamsters

Several intracellular Leishmania antigens have been identified in order to find a potential vaccine capable of conferring long lasting protection against Leishmania infection. Histones and Acid Ribosomal proteins are already known to induce an effective immune response and have successfully been tested in the cutaneous leishmaniasis mouse model. Here, we investigate the protective ability of L. infantum nucleosomal histones (HIS) and ribosomal acidic protein P0 (LiP0) against L. infantum infection in the hamster model of visceral leishmaniasis using two different strategies: homologous (plasmid DNA only) or heterologous immunization (plasmid DNA plus recombinant protein and adjuvant). Immunization with both antigens using the heterologous strategy presented a high antibody production level while the homologous strategy immunized group showed predominantly a cellular immune response with parasite load reduction. The pcDNA-LiP0 immunized group showed increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β in the lymph nodes before challenge. Two months after infection hamsters immunized with the empty plasmid presented a pro-inflammatory immune response in the early stages of infection with increased expression ratio of IFN-γ/IL-10 and IFN-γ/TGF-β, whereas hamsters immunized with pcDNA-HIS presented an increase only in the ratio IFN-γ/ TGF-β. On the other hand, hamsters immunized with LiP0 did not present any increase in the IFN-γ/TGF-β and IFN-γ/IL-10 ratio independently of the immunization strategy used. Conversely, five months after infection, hamsters immunized with HIS maintained a pro-inflammatory immune response (ratio IFN-γ/ IL-10) while pcDNA-LiP0 immunized hamsters continued showing a balanced cytokine profile of pro and anti-inflammatory cytokines. Moreover we observed a significant reduction in parasite load in the spleen, liver and lymph node in this group compared with controls. Our results suggest that vaccination with L. infantum LiP0 antigen administered in a DNA formulation could be considered a potential component in a vaccine formulation against visceral leishmaniasisThis study was funded by CNPq and CYTED. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscrip

Inmunología en el diagnóstico, patogénesis, tratamiento y prevención por las vacunas contra el COVID-19

A pandemia de covid-19 causada pelo SARS-CoV-2 destacou os riscos cada vez mais frequentes das mudanças significativas na Terra. Tanto o aquecimento global, por alterar os ecossistemas, quanto o aumento da mobilidade, promovendo o contato rápido e regular entre as populações em diferentes regiões, estão implicados no surgimento de surtos epidêmicos e pandemias. Ao longo deste evento, a ciência desempenhou um papel proeminente, evidente em vários campos. A biologia promoveu o rápido conhecimento sobre o SARS-CoV-2 e a epidemiologia, ao estudar os padrões de transmissão do vírus e na disseminação da infecção. A matemática e a física contribuíram para a elaboração de modelos para prever a evolução da doença e o impacto das medidas não farmacológicas de contenção, e.g. Em múltiplas especialidades, as ciências da saúde como medicina, fisioterapia e enfermagem também estiveram em evidência. Neste texto, destacamos a contribuição da imunologia por meio de seu papel no campo do diagnóstico, na compreensão dos mecanismos da doença, que levam a métodos de tratamento mais eficazes, e no desenvolvimento de vacinas capazes de proteger contra o mencionado vírus.The COVID-19 pandemic, caused by SARS-CoV-2, highlighted the risks, more and more frequently, from the significant changes on Earth. Global warming, which alters ecosystems, and increased mobility by promoting rapid and regular contact between populations in different regions, are implicated in the emergence of epidemic outbreaks and pandemics. Throughout the COVID-19 pandemic, science played a prominent role. The role of science has been very much in evidence in several fields. In biology, it promoted the rapid knowledge of SARS-CoV-2, in epidemiology, by studying patterns of virus transmission and spread of infection. Mathematics and physics contributed to the elaboration of models to predict the evolution of the disease and the impact of non-pharmacological measures of containment, e.g. In multiple specialties, the health sciences such as medicine, physiotherapy, and nursing, among others, were in evidence. In this text, we highlight the contribution of immunology through its role in the fields of diagnosis, understanding the mechanisms of disease, which lead to more efficient treatment methods, and the development of vaccines capable of protecting against COVID-19.La pandemia de COVID-19, causada por el SARS-CoV-2, puso de relieve los riesgos, cada vez más frecuentes, de los cambios significativos en la Tierra. Tanto el calentamiento global, al alterar los ecosistemas, como el aumento de la movilidad, promoviendo un contacto rápido y regular entre poblaciones de diferentes regiones, están implicados en la aparición de brotes epidémicos y pandemias. Durante la pandemia de COVID-19, la ciencia jugó un papel destacado en varios campos. La biología permitió el rápido conocimiento del SARS-CoV-2 y la epidemiología el estudio de los patrones de transmisión de virus y propagación de la infección. Las matemáticas y la física aportaron la elaboración de modelos para predecir la evolución de la enfermedad y el impacto de las medidas de contención no farmacológicas, e. g. Las múltiples especialidades de las ciencias de la salud, como la medicina, la fisioterapia, o la enfermería, entre otras, también desempeñaron un papel evidente. En este texto, destacamos la contribución de la inmunología a través de su papel en los campos del diagnóstico, la comprensión de los mecanismos de la enfermedad, que conducen a métodos de tratamiento más eficientes, y el desarrollo de vacunas capaces de proteger contra el COVID-19

Imunologia no diagnóstico, patogênese, tratamento e prevenção pelas vacinas para a covid-19

The COVID-19 pandemic, caused by SARS-CoV-2, highlighted the risks, more and more frequently, from the significant changes on Earth. Global warming, which alters ecosystems, and increased mobility by promoting rapid and regular contact between populations in different regions, are implicated in the emergence of epidemic outbreaks and pandemics. Throughout the COVID-19 pandemic, science played a prominent role. The role of science has been very much in evidence in several fields. In biology, it promoted the rapid knowledge of SARS-CoV-2, in epidemiology, by studying patterns of virus transmission and spread of infection. Mathematics and physics contributed to the elaboration of models to predict the evolution of the disease and the impact of non-pharmacological measures of containment, e.g. In multiple specialties, the health sciences such as medicine, physiotherapy, and nursing, among others, were in evidence. In this text, we highlight the contribution of immunology through its role in the fields of diagnosis, understanding the mechanisms of disease, which lead to more efficient treatment methods, and the development of vaccines capable of protecting against COVID-19.La pandemia de COVID-19, causada por el SARS-CoV-2, puso de relieve los riesgos, cada vez más frecuentes, de los cambios significativos en la Tierra. Tanto el calentamiento global, al alterar los ecosistemas, como el aumento de la movilidad, promoviendo un contacto rápido y regular entre poblaciones de diferentes regiones, están implicados en la aparición de brotes epidémicos y pandemias. Durante la pandemia de COVID-19, la ciencia jugó un papel destacado en varios campos. La biología permitió el rápido conocimiento del SARS-CoV-2 y la epidemiología el estudio de los patrones de transmisión de virus y propagación de la infección. Las matemáticas y la física aportaron la elaboración de modelos para predecir la evolución de la enfermedad y el impacto de las medidas de contención no farmacológicas, e. g. Las múltiples especialidades de las ciencias de la salud, como la medicina, la fisioterapia, o la enfermería, entre otras, también desempeñaron un papel evidente. En este texto, destacamos la contribución de la inmunología a través de su papel en los campos del diagnóstico, la comprensión de los mecanismos de la enfermedad, que conducen a métodos de tratamiento más eficientes, y el desarrollo de vacunas capaces de proteger contra el COVID-19.A pandemia de covid-19 causada pelo SARS-CoV-2 destacou os riscos cada vez mais frequentes das mudanças significativas na Terra. Tanto o aquecimento global, por alterar os ecossistemas, quanto o aumento da mobilidade, promovendo o contato rápido e regular entre as populações em diferentes regiões, estão implicados no surgimento de surtos epidêmicos e pandemias. Ao longo deste evento, a ciência desempenhou um papel proeminente, evidente em vários campos. A biologia promoveu o rápido conhecimento sobre o SARS-CoV-2 e a epidemiologia, ao estudar os padrões de transmissão do vírus e na disseminação da infecção. A matemática e a física contribuíram para a elaboração de modelos para prever a evolução da doença e o impacto das medidas não farmacológicas de contenção, e.g. Em múltiplas especialidades, as ciências da saúde como medicina, fisioterapia e enfermagem também estiveram em evidência. Neste texto, destacamos a contribuição da imunologia por meio de seu papel no campo do diagnóstico, na compreensão dos mecanismos da doença, que levam a métodos de tratamento mais eficazes, e no desenvolvimento de vacinas capazes de proteger contra o mencionado vírus

New Insights on the Inflammatory Role of Lutzomyia longipalpis Saliva in Leishmaniasis

When an haematophagous sand fly vector insect bites a vertebrate host, it introduces its mouthparts into the skin and lacerates blood vessels, forming a hemorrhagic pool which constitutes an intricate environment of cell interactions. In this scenario, the initial performance of host, parasite, and vector “authors” will heavily influence the course of Leishmania infection. Recent advances in vector-parasite-host interaction have elucidated “co-authors” and “new roles” not yet described. We review here the stimulatory role of Lutzomyia longipalpis saliva leading to inflammation and try to connect them in an early context of Leishmania infection

Leishmanial infection: analysis of its first steps. A review

The first steps in leishmaniasis are critical in determining the evolution of the disease. Major advances have recently been done in understanding this crucial moment. Fundamental research in parasite-vector interaction, parasite biology, insect saliva, and vertebrate host response have shed new light and uncovered a most fascinating and complex moment in leishmaniasis. We review here some of these aspects and we try to connect them in a logical framework

Balance of IL-10 and Interferon-γ plasma levels in human visceral leishmaniasis: Implications in the pathogenesis

BACKGROUND: Leishmaniasis remains a serious public health problem in several parts of the developing world. Effective prophylactic measurements are hampered by imprecise comprehension of different aspects of the disease, including its immunoregulation. A better comprehension of immunoregulation in human VL may be useful both for designing and evaluating immunoprophylaxis. METHODS: To explore immunoregulatory mechanisms, 20 visceral leishmaniasis (VL) patients were evaluated during active disease and at different periods up to one year after treatment determining their plasma cytokine levels, clinical parameters (palpable spleen and liver) and antibody levels. RESULTS: Elevated plasma levels of IFN-γ and of IL-12 p40 were observed during active disease, significantly decreasing after treatment whereas in vitro Leishmania antigen-stimulated IFN-γ production by PBMC exhibited an inverse pattern being low during disease and increasing steadily thereafter. Absence of IFN-γ activity is a hallmark of VL. The main candidate for blunting IFN-γ activity is IL-10, a cytokine highly elevated in plasma with sharp decrease after treatment. Activity of IL-10 is inferred by high levels of anti-Leishmania specific IgG1 and IgG3. TGF-β had elevated total, but not of active, levels lessening the likelihood of being the IFN-γ counterpart. Spleen or liver size presented a steady decrease but return to normal values at only 120 days after treatment. Anti-Leishmania IgG (total and subclasses) levels and DTH or Leishmania-stimulated lymphocyte proliferation conversion to positive also present a slow decrease after treatment. IL-6 plasma levels were elevated in only a few patients. CONCLUSION: Taken together our results suggest that IFN-γ and IL-10 are the molecules most likely involved in determining fate of disease. After treatment, there is a long delay before the immune profile returns to normal what precludes using plasma cytokine levels as criteria of cure as simpler clinical evaluations, as a palpable spleen or liver, can be used

Severe Plasmodium vivax malaria exhibits marked inflammatory imbalance

<p>Abstract</p> <p>Background</p> <p>Despite clinical descriptions of severe vivax malaria cases having been reported, data regarding immunological and inflammatory patterns are scarce. In this report, the inflammatory and immunological status of both mild and severe vivax malaria cases are compared in order to explore immunopathological events in this disease.</p> <p>Methods and Results</p> <p>Active and passive malaria case detections were performed during 2007 in Buritis, Rondônia, in the Brazilian Amazon. A total of 219 participants enrolled the study. Study individuals were classified according to the presence of <it>Plasmodium vivax </it>infection within four groups: non-infected (n = 90), asymptomatic (n = 60), mild (n = 50) and severe vivax infection (n = 19). A diagnosis of malaria was made by microscopy and molecular assays. Since at present no clear criteria define severe vivax malaria, this study adapted the consensual criteria from falciparum malaria. Patients with severe <it>P. vivax </it>infection were younger, had lived for shorter time in the endemic area, and recalled having experienced less previous malaria episodes than individuals with no malaria infection and with mild or asymptomatic infection. Strong linear trends were identified regarding increasing plasma levels of C reactive protein (CRP), serum creatinine, bilirubins and the graduation of disease severity. Plasma levels of tumour necrosis factor (TNF), interferon-gamma(IFN-gamma) and also IFN-gamma/interleukin-10 ratios were increased and exhibited a linear trend with gradual augmentation of disease severity. Both laboratory parameters of organ dysfunction and inflammatory cytokines were reduced during anti-parasite therapy in those patients with severe disease.</p> <p>Conclusion</p> <p>Different clinical presentations of vivax malaria infection present strong association with activation of pro-inflammatory responses and cytokine imbalance. These findings are of utmost importance to improve current knowledge about physiopathological concepts of this serious widespread disease.</p

BALB/c Mice Vaccinated with Leishmania major Ribosomal Proteins Extracts Combined with CpG Oligodeoxynucleotides Become Resistant to Disease Caused by a Secondary Parasite Challenge

Leishmaniasis is an increasing public health problem and effective vaccines are not currently available. We have previously demonstrated that vaccination with ribosomal proteins extracts administered in combination of CpG oligodeoxynucleotides protects susceptible BALB/c mice against primary Leishmania major infection. Here, we evaluate the long-term immunity to secondary infection conferred by this vaccine. We show that vaccinated and infected BALB/c mice were able to control a secondary Leishmania major challenge, since no inflammation and very low number of parasites were observed in the site of reinfection. In addition, although an increment in the parasite burden was observed in the draining lymph nodes of the primary site of infection we did not detected inflammatory lesions at that site. Resistance against reinfection correlated to a predominant Th1 response against parasite antigens. Thus, cell cultures established from spleens and the draining lymph node of the secondary site of infection produced high levels of parasite specific IFN-γ in the absence of IL-4 and IL-10 cytokine production. In addition, reinfected mice showed a high IgG2a/IgG1 ratio for anti-Leishmania antibodies. Our results suggest that ribosomal vaccine, which prevents pathology in a primary challenge, in combination with parasite persistence might be effective for long-term maintenance of immunity

Живопись викторианской эпохи в Англии. История создания прерафаэлитского братства

В статье рассматривается история возникновения и развития братства Прерафаэлитов. Анализируется творчество художников: Данте Россетти, Холмана Ханта, Джона Миллеса.У статті розглядається історія виникнення та розвитку братства Прерафаелітів. Аналізується творчість митців: Данте Россетті, Холмана Ханта, Джона Міллеса.The foundation and development of the Pre-Raphaelites Brotherhood is observed in the article. The life and main works of the following artists are analyzed: Dante Gabriel Rossetti, William Holman Hunt and John Everett Millais