CD39 expression by regulatory T cells participates in CD8+ T cell suppression during experimental Trypanosoma cruzi infection.

An imbalance between suppressor and effector immune responses may preclude cure in chronic parasitic diseases. In the case of Trypanosoma cruzi infection, specialized regulatory Foxp3+ T (Treg) cells suppress protective type-1 effector responses. Herein, we investigated the kinetics and underlying mechanisms behind the regulation of protective parasite-specific CD8+ T cell immunity during acute T. cruzi infection. Using the DEREG mouse model, we found that Treg cells play a role during the initial stages after T. cruzi infection, restraining the magnitude of CD8+ T cell responses and parasite control. Early Treg cell depletion increased the frequencies of polyfunctional short-lived, effector T cell subsets, without affecting memory precursor cell formation or the expression of activation, exhaustion and functional markers. In addition, Treg cell depletion during early infection minimally affected the antigen-presenting cell response but it boosted CD4+ T cell responses before the development of anti-parasite effector CD8+ T cell immunity. Crucially, the absence of CD39 expression on Treg cells significantly bolstered effector parasite-specific CD8+ T cell responses, preventing increased parasite replication in T. cruzi infected mice adoptively transferred with Treg cells. Our work underscores the crucial role of Treg cells in regulating protective anti-parasite immunity and provides evidence that CD39 expression by Treg cells represents a key immunomodulatory mechanism in this infection model.

CD39+ conventional CD4+ T cells with exhaustion traits and cytotoxic potential infiltrate tumors and expand upon CTLA-4 blockade.

Conventional CD4+ T (Tconv) lymphocytes play important roles in tumor immunity; however, their contribution to tumor elimination remains poorly understood. Here, we describe a subset of tumor-infiltrating Tconv cells characterized by the expression of CD39. In several mouse cancer models, we observed that CD39+ Tconv cells accumulated in tumors but were absent in lymphoid organs. Compared to tumor CD39- counterparts, CD39+ Tconv cells exhibited a cytotoxic and exhausted signature at the transcriptomic level, confirmed by high protein expression of inhibitory receptors and transcription factors related to the exhaustion. Additionally, CD39+ Tconv cells showed increased production of IFNγ, granzyme B, perforin and CD107a expression, but reduced production of TNF. Around 55% of OVA-specific Tconv from B16-OVA tumor-bearing mice, expressed CD39. In vivo CTLA-4 blockade induced the expansion of tumor CD39+ Tconv cells, which maintained their cytotoxic and exhausted features. In breast cancer patients, CD39+ Tconv cells were found in tumors and in metastatic lymph nodes but were less frequent in adjacent non-tumoral mammary tissue and not detected in non-metastatic lymph nodes and blood. Human tumor CD39+ Tconv cells constituted a heterogeneous cell population with features of exhaustion, high expression of inhibitory receptors and CD107a. We found that high CD4 and ENTPD1 (CD39) gene expression in human tumor tissues correlated with a higher overall survival rate in breast cancer patients. Our results identify CD39 as a biomarker of Tconv cells, with characteristics of both exhaustion and cytotoxic potential, and indicate CD39+ Tconv cells as players within the immune response against tumors.

Interleukin-17 signaling influences CD8+ T cell immunity and tumor progression according to the IL-17 receptor subunit expression pattern in cancer cells.

IL-17 immune responses in cancer are controversial, with both tumor-promoting and tumor-repressing effects observed. To clarify the role of IL-17 signaling in cancer progression, we used syngeneic tumor models from different tissue origins. We found that deficiencies in host IL-17RA or IL-17A/F expression had varying effects on the in vivo growth of different solid tumors including melanoma, sarcoma, lymphoma, and leukemia. In each tumor type, the absence of IL-17 led to changes in the expression of mediators associated with inflammation and metastasis in the tumor microenvironment. Furthermore, IL-17 signaling deficiencies in the hosts resulted in decreased anti-tumor CD8+ T cell immunity and caused tumor-specific changes in several lymphoid cell populations. Our findings were associated with distinct patterns of IL-17A/F cytokine and receptor subunit expression in the injected tumor cell lines. These patterns affected tumor cell responsiveness to IL-17 and downstream intracellular signaling, leading to divergent effects on cancer progression. Additionally, we identified IL-17RC as a critical determinant of the IL-17-mediated response in tumor cells and a potential biomarker for IL-17 signaling effects in tumor progression. Our study offers insight into the molecular mechanisms underlying IL-17 activities in cancer and lays the groundwork for developing personalized immunotherapies.

Actualización general de inmunoterapia en cáncer / Cancer immunotherapy: an update

Cancer is one of the leading causes of death worldwide. The success rate of conventional anticancer therapeutic approaches such as chemotherapy is limited by the non-specific toxicity and low specificity towards specific tumors, which are highly dependent on the mutational burden present on each patient. Similarly, targeted therapies have proven to induce resistance in numerous malignancies. Therefore, immunotherapy has emerged as a better approach to discriminate between "the own" and "the non-own", which occurs through two types of mechanisms, innate and acquired immunity. Acquired immunity is one of the targets for new immunotherapeutic treatments, unleashing the power of antigen-specific T cells as a potential therapeutic weapon for cancer treatment. Thus, immunotherapy modifies the own immune system to increase the recognition and elimination of cancer cells by identifying these cancer antigens. One of the advantages of immunotherapy, when compared to conventional anticancer approaches, is the generation of long-term immunity (immunological memory). Currently, there are different potential types of immunotherapy in cancer to promote the modulation of the immune response. Among them, the use of cytokines, vaccines, viruses, monoclonal antibodies, and the generation of adaptive immune response cells have achieved successful results in some types of cancer.

Interleukin-17 mediated immunity during infections with Trypanosoma cruzi and other protozoans.

Host resistance during infection with Trypanosoma cruzi, and other protozoans, is dependent on a balanced immune response. Robust immunity against these pathogens requires of the concerted action of many innate and adaptive cell populations including macrophages, neutrophils, dendritic cells, CD4+, and CD8+ T cells and B cells among others. Indeed, during most protozoan infections only a balanced production of inflammatory (TH1) and anti-inflammatory (TH2/regulatory) cytokines will allow the control of parasite spreading without compromising host tissue integrity. The description of TH17 cells, a novel effector helper T cell lineage that produced IL-17 as signature cytokine, prompted the revision of our knowledge about the mechanisms that mediate protection and immunopathology during protozoan infections. In this manuscript we discuss the general features of IL-17 mediated immune responses as well as the cellular sources, effector mechanisms and overall role of IL-17 in the immune response to T. cruzi and other protozoan infections.

[Cancer immunotherapy: an update]. / Actualización general de inmunoterapia en cáncer.

Cancer is one of the leading causes of death worldwide. The success rate of conventional anticancer therapeutic approaches such as chemotherapy is limited by the non-specific toxicity and low specificity towards specific tumors, which are highly dependent on the mutational burden present on each patient. Similarly, targeted therapies have proven to induce resistance in numerous malignancies. Therefore, immunotherapy has emerged as a better approach to discriminate between "the own" and "the non-own", which occurs through two types of mechanisms, innate and acquired immunity. Acquired immunity is one of the targets for new immunotherapeutic treatments, unleashing the power of antigen-specific T cells as a potential therapeutic weapon for cancer treatment. Thus, immunotherapy modifies the own immune system to increase the recognition and elimination of cancer cells by identifying these cancer antigens. One of the advantages of immunotherapy, when compared to conventional anticancer approaches, is the generation of long-term immunity (immunological memory). Currently, there are different potential types of immunotherapy in cancer to promote the modulation of the immune response. Among them, the use of cytokines, vaccines, viruses, monoclonal antibodies, and the generation of adaptive immune response cells have achieved successful results in some types of cancer.

Control del deterioro microbiológico de filetes de tilapia mediante la aplicación de bacterias lácticas / Control Microbiological Deterioration of Tilapia Fillets by the Application of Lactic Acid Bacteria / Controle de Deterioração Microbiológica da Tilápia Arquiva Através da Aplicação de Bactérias Láticas

Resumen En los últimos años se ha reconocido el potencial de las bacterias ácido lácticas (BAL) como agentes bioconservantes de productos cárnicos, incluido el pescado, al reducir el deterioro microbiológico y químico. El objetivo de este trabajo fue determinar el efecto bioconservante de dos cepas de BAL y el tiempo de impregnación en la calidad microbiológica y química de filetes de tilapia. Se evaluaron dos tiempos de impregnación (1h y 2h) y las BAL Lactobacillus plantarum JCM 1149 y Lactobacillus acidophilus ATCC4356. Los filetes bioconservados (FB) se almacenaron a 5°C y se evaluaron los cambios en el recuento de BAL, mesófilos, psicrófilos y coliformes totales durante 30 días. Los recuentos en los FB fueron de 5.94 de Log UFC/g. de BAL, y <2.7 log UFC/g de coliformes y psicrófilos. Los filetes control presentaron recuentos de 1.2 log UFC/g de BAL mientras los coliformes totales y psicrófilos superaron el límite permitido para consumo humano luego de 10 días. Luego de 10 días. El tratamiento que mantuvo la calidad microbiológica y química de los FB por más tiempo fue L. plantarum con inmersión de una hora. Las BAL estudiadas mostraron un efecto inhibitorio de la microflora deteriorante del pescado y una reducción en la formación de nitrógeno volátil, siendo un método viable para la conservación del pescado.

Abstract In recent years, it has recognized the potential of lactic acid bacteria (LAB) as biopreservatives agents for meat products, including fish, by reducing the microbiological and chemical spoilage. The aim of this study was to determine the effect of two strains biopreservative LAB and impregnation time on the microbiological and chemical quality of tilapia fillets. Two impregnation time (1h and 2h) and two LAB (Lactobacillus plantarum JCM 1149 and Lactobacillus acidophilus ATCC4356 were evaluated. The biopreserved fillets (BF) were stored at 5 ° C and the changes of the LAB count, mesophilic, psychrophilic and total coliforms., were evaluated for 30 days. The microbiological analysis show for the BF 5.94 log CFU / g. of LAB and <2.7 log CFU / g of coliform and psychrophilic bacteria. The control Fillets showed 1.2 log CFU / g of LAB while the psychrophile and total coliforms exceeded the allowed limit for human consumption after 10 days. The treatment kept the microbiological and chemical quality of the BF longer was L. plantarum with one hour of impregnation. The LAB studied showed an inhibitory effect of the spoilage microflora of fish and a reduction in the formation of volatile nitrogen compounds, being a viable fish preservation method.

Resumo Nos últimos anos tem se reconhecido o potencial das bactérias ácido lácticas (BAL) como agentes bioconservantes de pro dutos carnicos, incluído o peixe ao diminuir o deterioro microbiológico e químico. O propósito deste estudo foi determinar o efeito bioconservante de duas cepas de BAL e a avaliação do tempo de impregnação requerido para obter uma boa qua lidade microbiológica e química de filetes de tilapia. Foram avaliados dois tempos de impregnação (1h e 2h) com as BAL Lactobacillus plantarum JMC 1149 e Lactobacillus acidophilus ATCC4356. Os filetes biopreservados (FB) foram estocados a 5oC e valoradas as modificações na contagem de microorganismos BAL, mesófilos, psicrófilos, coliformes totais durante 30 dias. As contagens microbianas nos FB foram de 5.94 de log UFC/g e <2.7 log UFC/g de coliformes e psicrofilos. Os filetes controle apresentaram valores de 1.2 log UFC/g de BAL, não entanto os coliformes totais e psicrófilos superaram o limite permitido para consumo humano após 10 dias de estocagem. O tratamento que manteve a qualidade microbiológica e química dos FB por maior tempo foi de imersão com Lactobacillus plantarum por uma hora. As BAL estudadas amostraram um efeito inibitório da microflora deteriorante dos peixes e uma redução na formação de nitrogênio volátil se apresentan do como um método viável para a preservação de filete de peixe

La variable de discapacidad en la política cultural en Chile: balances y desafíos / The disability variable in Chilean cultural policy: evaluation and challenges

Introducción: el origen de la discapacidad no se encuentra únicamente en el individuo, sino que en la interacción negativa entre factores individuales y contextuales. Estos últimos determinan barrera su oportunidades de participación y al variar, pueden modificar la condición de discapacidad e incluso eliminarla aún cuando el individuo mantenga su diagnóstico de salud. De aquí la vinculación y la importancia de las acciones de la política pública en torno a la temática. Esta investigación, pondrá su foco en la Política Cultural de Chile la cual establece entre sus principios la promoción del acceso y la participación de la comunidad en iniciativas artístico - culturales, lo que sin duda incluye la variable discapacidad. Objetivo: El objetivo de la investigación es contribuir a la vinculación efectiva y apropiada entre la variable discapacidad y el acceso a la cultura desde las políticas públicas chilenas, explorando desafíos para la gestión cultural en esta materia. Metodología: Basándose en el concepto de accesibilidad universal, y con una metodología de tipo cualitativa, se analizan los programas de política pública asociados a la variable discapacidad de tres servicios del Estado:Dirección de Bibliotecas Archivos y Museos, el Servicio Nacional de Discapacidad y el Consejo Nacional de la Cultura y las Artes. Resultados:Se evidencia luego de realizados los análisis, que si bien desde el Estado chileno se integran líneas que abordan temas de discapacidad y cultura, lo que sin duda debe ser reconocido como un avance, estas referencias no garantizan de manera óptima la accesibilidad universal. Conclusion: El gestor cultural aparece como un actor relevante en la formulación de la política cultural y por tanto en la construcción de la situación de discapacidad.

Introduction: the origin of the disability is not only in the individual. It is on the interaction between individual and contextual factors and these last ones determine opportunities of participation. When factors are varying, they can modify the condition of disability and eliminate it, even if the person maintains his diagnosis of health. In this sense, public policies are important to address the issue. This research will focus on the Chilean Cultural Policy, which establishes among its principles: the promotion of access and participation of the community in a rtistic and cultural initiatives. It is included the variable disability, undoubtedly. Objetive: The objective of the research is to contribute to the effective and appropriate link between the variables “disability” and “access to culture” from public policies, exploring cultural management challenges. Methodology: Based on the concept of universal accessibility, this research has a Methodology of qualitative type. It analyses the public policy programs associated with the variable disability of three State services: Directorate of Libraries, Archives and Museums, National Disability Service and National Council of Culture and Arts. Results:It is evident from the analysis that references of disability and culture are integrated by the Chilean State, and it should certainly be recognized as an advance, but these references do not guarantee the optimum universal accessibility. Conclusions: The cultural manager appears as a relevant actor in the formulation of cultural policy and therefore in the construction of the disability situation.

Utilidad de la cromoendoscopia sistemática en el diagnóstico del cáncer temprano y lesiones gástricas premalignas. Resultado de dos campañas masivas consecutivas de tamización en Colombia (2006-2007) / Effectiveness of systematic chromoendoscopy for diagnosis of early cancer and gastric premalgnant lesions. Results of two consecutive screening campaigns in Colombia (2006-2007)

Introducción: El cáncer gástrico es la malignidad más común en América del Sur y Asia oriental. En Colombia, aparte del grave problema de mortalidad, una limitante es la escasez de datos de prevalencia de lesiones tempranas y premalignas. Objetivos y métodos: Evaluar la utilidad de la cromoendoscopia sistemática en la prevalencia de de cáncer gástrico temprano y lesión gástrica pre-maligna. Un total de 950 sujetos fueron convocados. 800 sujetos cumplieron los criterios de inclusión y finalmente 650 fueron analizados. Resultados: Ninguno de los participantes presentó mucosa gástrica normal. Gastritis antral crónica leve se encontró en 21,8% (142/650) mientras que gastritis antral crónica moderada o severa se encontró en el 77,4% (508/650). Atrofia y metaplasia fue encontrada en 14,5% (94/650) y 15,5% (101/650) respectivamente. Infección por H. Pylori en 7,3%, 79,3% 75,5% 57,4% y 0% de los sujetos con gastritis antral leve, gastritis moderada o severa, atrofia, metaplasia y displasia respectivamente. Lesión gástrica premaligna en 30% (195/650). Dos participantes fueron diagnosticados con cáncer gástrico temprano y tratados curativamente con disección endoscópica de la submucosa. Conclusión: Utilizando cromoendoscopia sistemática esta serie ha demostrado que uno de 325 voluntarios sanos tiene cáncer gástrico temprano, y 1 de cada 33 tiene lesión gástrica premaligna explicando así la alta prevalencia de cáncer gástrico avanzado en la región. En voluntarios sanos de Colombia el cáncer gástrico temprano es diagnosticable y curable.

Indroduction: Gastric cancer is the most common maligancy in South America and East Asia. In addition to the high mortality, in Colombia a great disvantage is the lack of data regarding premalignant lesions and early cancer. Aim: To evaluate the usefulness of systematic chromoendoscopy in the prevalence of early cancer and gastric premalignant lesions. A total of 950 were invited to participate, 800 fulfilled the inclusion criteria and finally 650 were analyzed. Results: None of participants had normal gastric mucosa. Mild antrum gastritis was found in 21.8% (142/650), meanwhile moderate or severe antrum gastritis in 77.4% (508/650). Atrophy and metaplasia was found in 14.5% (94/650) and 15.5% (101/650) respectively. H Pilory infection was found in 7.3%, 79.3% 75.5% 57.4% y 0% of subjects with mild, moderate and severe, atrophy, metaplasia and dysplasia respectively. Gastric premalignant lesion was found in 30% (195/650). Two subjects were diagnosed as early gastric cancer and treated by endoscopic submucosal dissection (ESD) with curability as final result. Conclusions: By systematic chromoendoscopy this series has demonstrated that 1/325 healthy volunteers had early gastric cancer and that 1/33 had a premalignant lesion explaining in part the high prevalence of gastric cancer in the region. Bases on this series, gastric cancer is diagnosable and curable among healthy volunteers in Colombia.

Estandarización de metodologías analíticas en el laboratorio de salud pública / Standardization of analytical methodologies in the public health laboratory

Objetivo Planear, diseñar y ejecutar la estandarización de las metodologías analíticas cuyo montaje se ha realizado con anterioridad. Métodos Una vez establecido el método de ensayo se realiza un análisis preliminar de reproducibilidad y un análisis de interferencia por matriz, para luego realizar la validación y calcular los atributos del método. Resultados En el Laboratorio de Salud Pública se estandarizaron trece métodos analíticos a los cuales se les calcularon los atributos de: límite de detección, límite de cuantificación, exactitud, precisión, sensibilidad y rango útil. Conclusiones Se determinó la alta confiabilidad de las pruebas analíticas del Laboratorio de Salud Pública para la generación de intervenciones sanitarias.

Objective To plan, design and execute the standardization of analytical methodologies that have been previously assembled. Methods Once the test method has been established, a preliminary reproducibility analysis and a matrix interference analysis are performed, and then the validation and calculation of the method attributes are carried out. Results Thirteen analytical methods were standardized in the Public Health Laboratory and the following attributes were calculated: limit of detection, limit of quantification, accuracy, precision, sensitivity and useful range. Conclusions The high reliability of the analytical tests of the Public Health Laboratory for the generation of health interventions was determined.