IL-22 Protects Against Liver Pathology and Lethality of an Experimental Blood-Stage Malaria Infection

The host response following malaria infection depends on a fine balance between levels of pro-inflammatory and anti-inflammatory mediators resulting in the resolution of the infection or immune-mediated pathology. Whilst other components of the innate immune system contribute to the pro-inflammatory milieu, T cells play a major role. For blood-stage malaria, CD4+ and γδ T cells are major producers of the IFN-γ that controls parasitemia, however, a role for TH17 cells secreting IL-17A and other cytokines, including IL-17F and IL-22 has not yet been investigated in malaria. TH17 cells have been shown to play a role in some protozoan infections, but they also are a source of pro-inflammatory cytokines known to be involved in protection or pathogenicity of infections. In the present study, we have investigated whether IL-17A and IL-22 are induced during a Plasmodium chabaudi infection in mice, and whether these cytokines contribute to either protection or to pathology induced during the infection. Although small numbers of IL-17- and IL-22-producing CD4 T cells are induced in the spleens of infected mice, a more pronounced induction is observed in the liver, where increases in mRNA for IL-17A and, to a lesser extent, IL-22 were observed and CD8+ T cells, rather than CD4 T cells, are a major source of these cytokines in this organ. Although the lack of IL-17 did not affect the outcome of infection or pathology, lack of IL-22 resulted in 50% mortality within 12 days after infection with significantly greater weight loss at the peak of infection and significant increase in alanine transaminase in the plasma in the acute infection. As parasitemias and temperature were similar in IL-22 KO and wild-type control mice, our observations support the idea that IL-22 but not IL-17 provides protection from the potentially lethal effects of liver damage during a primary P. chabaudi infection

Crescimento de plantas de tectona grandis sob restrição hídrica

O presente estudo teve como objetivo identificar a(s) estratégia(s) de sobrevivência de plantas de Tectona grandis sob déficit hídrico para fomentar programas de melhoramento genético. O trabalho foi conduzido em casa de vegetação coberta com plástico transparente e laterais fechadas com sombrite 50%. As sementes de Tectona grandis foram semeadas em vasos de 12 litros contendo uma mistura de solo, areia e esterco na proporção de 3:1:0,5 respectivamente. Utilizou-se o delineamento experimental inteiramente casualizado com cinco tratamentos e seis repetições. A partir do 101º dia após a germinação, as plantas foram submetidas a regimes hídricos diferenciais: plantas diariamente irrigadas com volume de água correspondente a 0%, 25%, 50%, 75% e 100% da evapotranspiração diária durante 20 dias e, em seguida, submetidas as análises. Em condição de déficit hídrico as plantas de Tectona grandis mantêm-se vivas com reduzido crescimento vegetativo, para tal, as plantas ajustam a área foliar e apresentam como estratégia de sobrevivência um eficiente mecanismo de fechamento estomático em função da elevada sensibilidade dos estômatos. O controle estomático da transpiração pode ser utilizado para pré-seleção de materiais promissores para programas de melhoramento genético

Metodologia para a avaliação da atividade física habitual em homens com 50 anos ou mais

OBJECTIVE: To describe the methodology for evaluating habitual physical activity that was adopted for a survey among the male population utilizing a questionnaire validated earlier. METHODS: The Baecke questionnaire on habitual physical activity was translated into Portuguese and then back-translated into English by two anglophone teachers. The final version of the questionnaire was applied in a cross-sectional epidemiological study done on 326 men aged 50 years or over. The internal consistency among the questions was evaluated using the Cronbach a statistic. The Spearman correlation coefficients between the habitual physical activity scores were calculated. Partial correlation coefficients with adjustments for age, body mass index and schooling were also calculated. RESULTS: There was satisfactory internal consistency in relation to the magnitudes of occupational physical activity and leisure-time physical exercises. Significant correlation was obtained between all the physical activity scores and the total habitual physical activity score, independent of age, body mass index and schooling. CONCLUSIONS: The Baecke questionnaire was found to be a practical instrument for assessing habitual physical activity that is quickly applied and easily understood, and it is recommended for epidemiological studies in Brazil.OBJETIVO: Descrever a metodologia de avaliação da atividade física habitual, utilizanda em uma pesquisa em população masculina, por meio de um questionário já validado. MÉTODOS: O questionário de atividade física habitual de Baecke, traduzido para a língua portuguesa e, a seguir, foi realizado o back translation. Em sua versão final o questionário foi aplicado em estudo epidemiológico transversal, realizado com 326 homens com idade igual ou superior a 50 anos. A consistência interna entre as questões foi analisada pelo a de Cronbach e foram calculados os coeficientes de correlação de Spearman entre os escores de atividade física habitual, bem como os coeficientes de correlação parcial, ajustados por idade, índice de massa corporal e escolaridade. RESULTADOS: A consistência interna mostrou-se satisfatória nas magnitudes de atividade física ocupacional e exercícios físicos no lazer. Foram obtidas correlações significativas entre todos os escores de atividades físicas com o escore total de atividade física habitual, independente da idade, escolaridade e índice de massa corporal. CONCLUSÕES: O questionário Baecke mostrou-se um instrumento prático para avaliar a atividade física habitual, aliando rapidez na aplicabilidade e facilidade no entendimento para as respostas, sendo indicado para estudos epidemiológicos no Brasil

Vulnerabilidades em saúde da criança durante a pandemia da COVID-19 no Brasil e em Portugal

Objetivo: : analisar as vulnerabilidades da criança no acesso aos cuidados na atenção primária durante a pandemia da COVID-19 no Brasil e em Portugal. Método: pesquisa documental baseada em diretrizes governamentais brasileiras e portuguesas, expedidas entre março e agosto de 2020, sobre o acesso de crianças à atenção primária. A análise temática fundamentou-se nos preceitos da vulnerabilidade em saúde. Resultados: expediram-se 13 documentos nos dois países sobre acesso à vacinação e à puericultura. A restrição à circulação do SARS-CoV-2 nos ambientes sociais, serviços de saúde e de proteção social reduziu a demanda de atendimento. Mantiveram-se, nos dois países, os programas de promoção da saúde do lactente. O acompanhamento de puericultura presencial, para crianças de baixo risco, foi suspenso nos dois países. Portugal manteve a vacinação rotineira e o Brasil a interrompeu nos primeiros 15 dias da pandemia. Os países adotaram estratégias remotas de atenção - telemonitoramento, teleconsulta e aplicativos móveis - mantendo o vínculo da criança com os serviços de saúde. Conclusão: a longitudinalidade foi afetada pela redução do acesso à promoção da saúde da criança, determinando maior vulnerabilidade programática. As vulnerabilidades individuais relacionaram-se à exposição a doenças evitáveis e sensíveis à atenção primária.Objetivo: analizar las vulnerabilidades del niño en el acceso a los cuidados en la atención primaria, durante la pandemia del COVID-19 en Brasil y Portugal. Método: investigación documental basada en directrices gubernamentales brasileñas y portuguesas, expedidas entre marzo y agosto de 2020, sobre el acceso de niños a la atención primaria. El análisis temático se fundamentó en los preceptos de la vulnerabilidad en la salud. Resultados: fueron encontrados 13 documentos, expedidos en los dos países, sobre el acceso a la vacunación y puericultura. La restricción de circulación del SARS-CoV-2 - en los ambientes sociales, servicios de salud y de protección social - redujo la demanda de la atención. En los dos países se mantuvieron los programas de promoción de la salud del lactante. El acompañamiento de puericultura presencial, para niños de bajo riesgo, fue suspendido en los dos países. Portugal mantuvo la vacunación de rutina y Brasil la interrumpió en los primeros 15 días de la epidemia. Los países adoptaron estrategias de atención a distancia (telemonitoreo, teleconsulta y aplicativos móviles) manteniendo el vínculo del niño con los servicios de la salud. Conclusión: la longitudinalidad fue afectada por la reducción del acceso a la promoción de la salud del niño, determinando mayor vulnerabilidad programática. Las vulnerabilidades individuales se relacionaron a la exposición a enfermedades evitables y sensibles a la atención primaria.Objective: to analyze the vulnerabilities of children in the access to primary health care during the COVID-19 pandemic in Brazil and Portugal. Method: documentary study based on Brazilian and Portuguese governmental guidelines issued between March and August 2020 regarding access of children to primary health care. Thematic analysis was based on the precepts of health vulnerability. Results: 13 documents were issued in both countries addressing access to vaccination and childcare. Due to the SARS-CoV-2, restrictions were imposed on the circulation of people in social environments, health services, and social protection, decreasing the demand for health services. Both countries continued programs to promote the health of breastfeeding infants. In-person childcare consultations were suspended for low-risk children in both countries. Portugal maintained routine vaccination while Brazil interrupted vaccination in the first 15 days of the pandemic. The countries adopted remote care strategies - telemonitoring, teleconsultation, and mobile applications - to maintain the bond between children and health services. Conclusion: longitudinality was affected due to restricted access of children to health promotion actions, determining greater programmatic vulnerability. Individual vulnerabilities are related to exposure to preventable and primary health care-sensitive diseases

Interferon-ß regulates the production of IL-10 by toll-like receptor-activated microglia

Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression. In this context, the anti-inflammatory cytokine interleukin (IL)-10 appears as an attractive target. In this study, we investigated how activation of microglia by TLRs with distinct roles in MS impacts on IL-10 production. We found that activation of TLR2, TLR4, and TLR9 induced the production of IL-10 to a greater extent than activation of TLR3. This was surprising as both TLR3 and IL-10 play protective roles in animal models of MS. Interestingly, combination of TLR3 triggering with the other TLRs, enhanced IL-10 through the modulation of its transcription, via interferon (IFN)-beta, but independently of IL-27. Thus, in addition to the modulation of inflammatory responses of the periphery described for the axis TLR3/IFN-beta, we now report a direct modulation of microglial responses. We further show that the presence of IFN-gamma in the microenvironment abrogated the modulation of IL-10 by TLR3, whereas that of IL-17 had no effect. Considering the therapeutic application of IFN-beta in MS, our study bears important implications for the understanding of the cytokine network regulating microglia responses in this setting.Portuguese Foundation for Science and Technology (FCT), Grant/Award Numbers: SFRH/BD/88081/2012 and SFRH/BPD/72710/2010; FEDER - Competitiveness Factors Operational Programme (COMPETE), Grant/Award Numbers: POCI-01-0145-FEDER-007038 and NORTE-01-0145-FEDER-000013; Norte Portugal Regional Operational Programme, PORTUGAL 2020, European Regional Development Fund (ERDF), Grant/Award Number: NORTE 2020; FCT-ANR, Grant/Award Number: FCT-ANR/BIM-MEC/0007/2013; FEDER - Fundo Europeu de Desenvolvimento Regional; COMPETE 2020 - Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; Institute for Research and Innovation in Health Sciences, Grant/Award Number: POCI-01-0145-FEDER-007274info:eu-repo/semantics/publishedVersio

One Episode of Self-Resolving Plasmodium yoelii Infection Transiently Exacerbates Chronic Mycobacterium tuberculosis Infection

Malaria and tuberculosis (Tb) are two of the main causes of death from infectious diseases globally. The pathogenic agents, Plasmodium parasites and Mycobacterium tuberculosis (Mtb), are co-endemic in many regions in the world however compared to other co-infections like HIV/Tb or helminth/Tb, malaria/Tb has been given less attention both in clinical and immunological studies. Due to the lack of sufficient human data, the impact of malaria on Tb and vice versa is difficult to estimate but co-infections are likely to occur very frequently. Due to its immunomodulatory properties malaria might be an underestimated risk factor for latent or active Tb patients particularly in high-endemic malaria settings were people experience reinfections very frequently. In the present study, we used the non-lethal strain of Plasmodium yoelii to investigate how one episode of self-resolving malaria impact on a chronic Mtb infection. P. yoelii co-infection resulted in exacerbation of Tb disease as demonstrated by increased pathology and cellular infiltration of the lungs which coincided with elevated levels of pro- and anti-inflammatory mediators. T cell responses were not impaired in co-infected mice but enhanced and likely contributed to increased cytokine production. We found a slight but statistically significant increase in Mtb burden in co-infected animals and increased lung CFU was positively correlated with elevated levels of TNFbut not IL-10. Infection with P. yoelii induced the recruitment of a CD11c+ population into lungs and spleens of Mtb infected mice. CD11c+ cells isolated from P. yoelii infected spleens promoted survival and growth of Mtb in vitro. 170 days after P. yoelii infection changes in immunopathology and cellular immune responses were no longer apparent while Mtb numbers were still slightly higher in lungs, but not in spleens of co-infected mice. In conclusion, one episode of P. yoelii co-infection transiently exacerbated disease severity but had no long-term consequences on disease progression and survival of Mtb infected mice

Effector Memory Th1 CD4 T Cells Are Maintained in a Mouse Model of Chronic Malaria

Protection against malaria often decays in the absence of infection, suggesting that protective immunological memory depends on stimulation. Here we have used CD4+ T cells from a transgenic mouse carrying a T cell receptor specific for a malaria protein, Merozoite Surface Protein-1, to investigate memory in a Plasmodium chabaudi infection. CD4+ memory T cells (CD44hiIL-7Rα+) developed during the chronic infection, and were readily distinguishable from effector (CD62LloIL-7Rα−) cells in acute infection. On the basis of cell surface phenotype, we classified memory CD4+ T cells into three subsets: central memory, and early and late effector memory cells, and found that early effector memory cells (CD62LloCD27+) dominated the chronic infection. We demonstrate a linear pathway of differentiation from central memory to early and then late effector memory cells. In adoptive transfer, CD44hi memory cells from chronically infected mice were more effective at delaying and reducing parasitemia and pathology than memory cells from drug-treated mice without chronic infection, and contained a greater proportion of effector cells producing IFN-γ and TNFα, which may have contributed to the enhanced protection. These findings may explain the observation that in humans with chronic malaria, activated effector memory cells are best maintained in conditions of repeated exposure

Regulation of immunity during visceral Leishmania infection

Unicellular eukaryotes of the genus Leishmania are collectively responsible for a heterogeneous group of diseases known as leishmaniasis. The visceral form of leishmaniasis, caused by L. donovani or L. infantum, is a devastating condition, claiming 20,000 to 40,000 lives annually, with particular incidence in some of the poorest regions of the world. Immunity to Leishmania depends on the development of protective type I immune responses capable of activating infected phagocytes to kill intracellular amastigotes. However, despite the induction of protective responses, disease progresses due to a multitude of factors that impede an optimal response. These include the action of suppressive cytokines, exhaustion of specific T cells, loss of lymphoid tissue architecture and a defective humoral response. We will review how these responses are orchestrated during the course of infection, including both early and chronic stages, focusing on the spleen and the liver, which are the main target organs of visceral Leishmania in the host. A comprehensive understanding of the immune events that occur during visceral Leishmania infection is crucial for the implementation of immunotherapeutic approaches that complement the current anti-Leishmania chemotherapy and the development of effective vaccines to prevent disease.The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED). VR is supported by a post-doctoral fellowship granted by the KINDReD consortium. RS thanks the Foundation for Science and Technology (FCT) for an Investigator Grant (IF/00021/2014). This work was supported by grants to JE from ANR (LEISH-APO, France), Partenariat Hubert Curien (PHC) (program Volubilis, MA/11/262). JE acknowledges the support of the Canada Research Chair Program