Rol de la microbiota gastrointestinal en la regulación de la respuesta inmune / The role of gut microbiota in the regulation of the immune response

The gastrointestinal tract hosts around 10(14) bacterial microorganisms, in a constantly growing density from the stomach to the distal colon. This microbiota is composed by more than 500 species of bacteria, which are quickly acquired after birth, fairly stable during the host’s life, and essential for human homeostasis. These bacteria have important functions, such as stimulating the immune system, protecting the host from invading bacteria and viruses, and improving digestion, especially of complex carbohydrates. Also, the gut microbiota interacts directly with the immune system. However, the interaction of the intestinal epithelium and its microbiota with the immune system has yet to be fully understood. Secretory immunoglobulin A, produced by the plasma cells in Peyer’s patches and in the lamina propria, maintains non-invasive commensal bacteria and neutralize invasive pathogens. Dendritic cells migrate from the lamina propria of the secondary lymphoid organs to regulate gut immunity. They also have a key role maintaining luminal IgA and inducing the growth of regulatory T cells. Dendritic cells supervise the gut microenvironment too, keeping an immunological equilibrium and tolerance. The importance of the gut microbiota in regulating the immune system lies mostly in the homeostasis-or positive equilibrium. Thus, many diseases are a consequence of poor interactions or a loss of this equilibrium.

Immune homeostasis to microorganisms in the guts of triatomines (Reduviidae): a review

Bacteria, fungi and parasites are in constant contact with the insect gut environment and can influence different aspects of the host gut physiology. Usually, some of these microorganisms develop and survive in the digestive tract. Therefore, the gut environment must be able to tolerate certain populations of these organisms for the establishment of interactions between non-pathogenic bacteria, parasites and the gut. This review provides a brief overview of the biological and molecular mechanisms that microorganisms use to interact with the gut epithelia in mosquitoes and speculates on their significances for the development of bacteria and Trypanosoma cruzi in the guts of triatomines.

Asociación de la insulina y el factor de crecimiento semejante a la insulina tipo 1 (IGF-1) en el cáncer de mama / Association between insulin and the insulin-like growth factor-I (IGF-I)in breast cancer

Con el objetivo de evaluar la asociación de la insulina y el factor de crecimiento insulino similar tipo 1 (IGF-1) en pacientes con cáncer de mama, se eligió una muestra de 15 pacientes con diagnóstico histopatológico de cáncer de mama durante el período enero-agosto de 2008, y se determinaron los niveles de glicemia en ayunas, insulina basal e IGF-1. Se evaluó el grado de insulino-sensibilidad mediante el método HOMA en esta muestra, comparándose posteriormente con pacientes sin cáncer y de edades similares. Encontramos que la concentración plasmática de insulina en las pacientes con cáncer fue de 11,53 ± 1,91 µU/mL; mientras que los controles presentaron 5,1 ± 0,98 µU/mL, lo cual resultó estadísticamente significativo (P<0,01). Además, las pacientes con cáncer de mama exhibieron glicemia de 108,57 ± 12,33 mg/dL, en comparación con los controles quienes obtuvieron 80,92 ± 1,40 mg/dL. Con estos resultados se calculó el HOMA, obteniendo valores de 3,15 y 1,00 respectivamente. Adicionalmente, al determinar IGF-1 observamos niveles de 219,64 ± 17,03 ng/mL en las pacientes con cáncer y de 178,47 ± 12,78 ng/mL en controles. Se concluye que las pacientes con cáncer de mama presentan el fenómeno de resistencia a la insulina, el cual de manera sinérgica con el IGF-1 promueve la proliferación y diferenciación de células mamarias

Samples from 15 patients who had been diagnosed with breast cancer during January-August 2008 were assayed for the purpose of evaluating the association of insulin and insulin-like growth factor-1 (IGF-1) in women with this type of cancer. Assays were performed to measure fasting blood glucose, basal insulin, and IGF-1. A homeostatic model assessment test (HOMA) was also performed to assess insulin sensitivity, and the results were matched against those of healthy women of the same age group. Insulin plasma concentration in the former group was 11.53 ± 1.91 µU/mL whereas that of the control group was 5.1 ± 0.98 µU/mL, a statistically significant finding. (P<0.01). In addition, the glucose level in the sick women was 108.57 ± 12.33 mg/dL as compared to 80.92 ± 1.40 mg/dL in those without cancer. HOMA was 3.15 and 1.00, and IGF.1 levels were 219.64 ± 17.03 ng/mL and 178.47 ± 12.78 ng/mL for sick and healthy women, respectively. It is thus concluded that women with cancer develop insulin resistance, which in synergy with IGF-1, promotes breast cell proliferation and differentiation

Impacto da administração intragástrica aguda de etanol sobre células apresentadoras de antígenos e linfócitos T Murinos

O consumo agudo do etanol exerce grande impacto sobre as atividades do sistema imune, levando a alterações que interferem na homeostase imunológica. As células apresentadoras de antígenos possuem um papel fundamental na determinação da função efetora de linfócitos T, direcionando o perfil dessas células para a tolerância ou para a inflamação. Alterações na distribuição e função das APCs podem comprometer ou estimular a geração de linfócitos T com características inflamatórias ou reguladoras. Utilizando um modelo agudo de administração de etanol descrito por Andrade e colaboradores (2006), demonstramos que os animais tratados com etanol apresentaram modificações funcionais relacionadas com uma menor produção de citocinas (IL-4, IL-12 e TNF-) por macrófagos, uma diminuição na atividade fagocitária e endocítica de macrófagos e células dendríticas, e interessantemente, um aumento na atividade endocítica de linfócitos B. Além disso, destacam-se alterações imunofenotípicas seletivas na população de macrófagos, relacionadas com a diminuição na. intensidade de expressão de CD40 e TLR-2. O consumo agudo do etanol repercutiu também sobre a população de linfócitos T, levando a um predomínio de um perfil inflamatório caracterizado pelo aumento de moléculas de ativação celular, como CD25, e por uma diminuição de moléculas associadas com atividades reguladoras em linfócitos T CD4+, tais como LAP e TLR-2. Em conjunto, acreditamos que as alterações imunofenotípicas e funcionais nas APCs após o tratamento com etanol, podem comprometer a geração de linfócitos T com atividades reguladoras e induzir o predomínio de um perfil celular inflamatório

Impacto da administração intragástrica aguda de etanol sobre células apresentadoras de antígenos e linfócitos T Murinos / Impact of acute intragastric administration of ethanol on antigen-presenting cells and T lymphocytes Murine

O consumo agudo do etanol exerce grande impacto sobre as atividades do sistema imune, levando a alterações que interferem na homeostase imunológica. As células apresentadoras de antígenos possuem um papel fundamental na determinação da função efetora de linfócitos T, direcionando o perfil dessas células para a tolerância ou para a inflamação. Alterações na distribuição e função das APCs podem comprometer ou estimular a geração de linfócitos T com características inflamatórias ou reguladoras. Utilizando um modelo agudo de administração de etanol descrito por Andrade e colaboradores (2006), demonstramos que os animais tratados com etanol apresentaram modificações funcionais relacionadas com uma menor produção de citocinas (IL-4, IL-12 e TNF-) por macrófagos, uma diminuição na atividade fagocitária e endocítica de macrófagos e células dendríticas, e interessantemente, um aumento na atividade endocítica de linfócitos B. Além disso, destacam-se alterações imunofenotípicas seletivas na população de macrófagos, relacionadas com a diminuição na. intensidade de expressão de CD40 e TLR-2. O consumo agudo do etanol repercutiu também sobre a população de linfócitos T, levando a um predomínio de um perfil inflamatório caracterizado pelo aumento de moléculas de ativação celular, como CD25, e por uma diminuição de moléculas associadas com atividades reguladoras em linfócitos T CD4+, tais como LAP e TLR-2. Em conjunto, acreditamos que as alterações imunofenotípicas e funcionais nas APCs após o tratamento com etanol, podem comprometer a geração de linfócitos T com atividades reguladoras e induzir o predomínio de um perfil celular inflamatório

La modulación del sistema inmune de mucosas con polisacáridos: Bases para una atractiva alternativa en terapia / Modulation of the mucosal immune system with polysaccharides: Basis for an attractive therapeutic alternative

El sistema inmune de mucosas del intestino presenta propiedades únicas: está expuesto a una gran variedad y cantidad de antígenos, desarrolla una actividad inmunológica permanente y mantiene un microambiente fisiológicamente desviado hacia respuestas anti-inflamatorias. Es capaz de distinguir y neutralizar agentes nocivos y reconocer antígenos inocuos, generando entonces un estado de no respuesta llamado tolerancia oral. Este fenómeno natural representa una forma fisiológica, segura e inocua de manipular las respuestas inmunes, para el tratamiento de enfermedades autoinmunes, inflamatorias o alérgicas. Aquellos compuestos que presenten la habilidad de favorecer la tolerancia permitirían optimizar el desarrollo de nuevos protocolos de inmunointervención. Quitosano (Q) es un polisacárido que abunda en la naturaleza con características fisicoquímicas y biológicas particulares: carece de toxicidad y alergenicidad, es biocompatible y biodegradable, presenta propiedades mucoadhesivas que favorecen el transporte y la absorción de proteínas a través del epitelio. Tiene actividad adyuvante, aumentando los niveles de IgA en la mucosa. Estas características lo convierten en un candidato ideal para la inmunointervención a nivel de mucosas. En este trabajo se describe el mecanismo de acción del Q luego de la administración oral, demostrando por primera vez que Q contribuye a mantener la homeostasis intestinal y a modular a nivel local y sistémico las respuestas inmunes hacia un antígeno proteico. Esta caracterización ayuda a comprender cómo participa un polisacárido en la fina regulación de las respuestas de mucosa y sugiere alternativas de manipulación que permitirán el desarrollo de terapias que requieran de microambientes anti-inflamatorios.

The mucosal immune system exhibits distinctive traits: it is permanently exposed to an overwhelming amount and variety of antigens; it maintains a continuous immune activity and it sustains a physiological environment biased to anti-inflammatory responses. Although it mounts efficient responses against pathogens, it reacts to innocuous antigens developing the oral tolerance state. Oral tolerance is a natural process that can be safely applied for the treatment of autoimmune, inflammatory or allergic diseases. Compounds able to promote the tolerance phenomenon can be used to optimize the development of alternative therapies. Chitosan (Q) is a natural and abundant polysaccharide with singular biological and physico-chemical properties that make it a good candidate to modulate the mucosal immunity: non toxic, biocompatible and biodegradable, strongly mucoadhesive favoring the transepithelial absorption of proteins and adjuvant, enhancing the levels of IgA to co-administered antigens. This work describes the Q activity mechanism early after its oral administration, for the first time showing, Q´s contribution to the intestinal homeostasis and also its modulation of the immune response to a protein antigen at local and systemic level. These studies will help understand how the intestinal regulatory activity occurs, and develop new therapeutic approaches to stimulate anti-inflammatory environments at mucosal level.

Maternal deprivation, acute respiratory infections and immune regulation.

OBJECTIVE: The study was designed to investigate the acute respiratory disease incidence (DI) in deprived infants and test the hypothesis if maternal deprivation effects the processes of immunoregulation in infants. METHODS: The prospective study during 1 year in Tbilisi Infant's House was performed. Cohort of 136 infants at age from 1 to 24 months without any congenital abnormalities formed the basic group. The cohort of 136 healthy infants at age 1 to 24 months of the same population living under the maternal care in three shelters of Tbilisi region was randomized as a control. The study included: DI, age of first attack, duration of illness, outcome, plasma immune parameters. RESULTS: The data have demonstrated that maternal deprivation induces a marked increase in the severity of acute respiratory disease among infants. DI was twice as much in deprived children as in control group. Moreover, there was diagnosed the disruption of normal correlations between plasma CD3, CD4 and CD8 in infants under maternal deprivation. CONCLUSION: Maternal deprivation induces changes in processes of immunoregulation in infants resulted in elevation of acute respiratory DI among them.

Apoptosis de linfocitos asociada a enfermedades infecciosas / [Lymphocyte apoptosis associated to infections]

During infections, the presence of lymphocyte apoptosis both in peripheral blood and in lymphatic organs has been described. This kind of programmed cell death can be either induced by host control mechanisms aimed at eliminating infected lymphocytes and/or retaining immune system homeostasis, or by the pathogen in order to complete its life cycle, spreading the infection and/or suppressing the immune response. Thus, apoptosis has advantages and disadvantages for the host depending on the pathogen life cycle and/or the specificity of the lymphocyte population affected. Identification of the mechanisms involved in autoreactive or pathogen-specific lymphocyte apoptosis could lead to strategies designed to interfere immunologically or pharmacologically in favor of the host.