New Insights into the Immunological Changes in IL-10-Deficient Mice during the Course of Spontaneous Inflammation in the Gut Mucosa

IL-10 is a regulatory cytokine that plays a major role in the homeostasis of the gut and this is illustrated by the fact that IL-10−/− mice develop spontaneous colitis. In this study, IL-10−/− mice were analyzed for immunological changes during colitis development. We found a reduced frequency of regulatory T cells CD4+CD25+Foxp3+ and higher frequency of activated T cells in the colon that precedes the macroscopic signs of the disease. Production of IL-17 and IFN-γ was higher in the colon. Colitis progression culminates with the reduction of CD4+LAP+ regulatory T cells in the intestine. Frequency of B1 cells and the secretory IgA production were both elevated. Despite these alterations, 16-week-old IL-10−/− mice could be rendered tolerant by a continuous feeding protocol. Our study provides detailed analysis of changes that precede colitis and it also suggests that oral tolerance could be used to design novel alternative therapies for the disease

Desarrollo de un entorno integrado para un computador didáctico elemental, para la asignatura de Fundamentos de Informática del nuevo grado en Ingeniería de Tecnologías de Telecomunicación

El objetivo principal de este trabajo es la potenciación y mejora de la metodología docente en la asignatura de Fundamentos de Informática, asignatura obligatoria correspondiente al nuevo Grado en Ingeniería de Tecnologías de Telecomunicación de la Universidad de Granada. Para ello, se ha desarrollado un entorno integrado didáctico que engloba, en una sola aplicación, tanto el simulador como el ensamblador de un Computador Didáctico Elemental desarrollado en nuestro departamento, CODE-2, y que, además, incorpora un programa editor y un ensamblador en línea con el que el alumno puede visualizar directamente el código máquina generado por el código ensamblador que está escribiendo en tiempo real. De esta forma, conseguimos facilitar que los alumnos puedan adquirir los conocimientos necesarios para comprender el funcionamiento interno de un computador.Subvencionado parcialmente por el proyecto de Innovación Docente 10-22 de la Universidad de Granad

New methodologies for the design of evolving fuzzy systems for online intelligent control

Tesis Univ. Granada. Departamento de Arquitectura y Tecnología de Computadores. Leída el 27 de marzo de 201

Food components and the Immune System: from tonic agents to allergens

The intestinal mucosa is the major site of contact with antigens, and it lodges the largest lymphoid tissue in the body. In physiological conditions, microbiota and dietary antigens are the natural sources of stimulation for the gut associated lymphoid tissues (GALT) and for the immune system as a whole. Germ free models have provided some insights on the immunological role of gut antigens. However, most of the GALT is not located in the large intestine, where gut microbiota is prominent. It is concentrated in the small intestine where protein absorption takes place. In this review, we will address the involvement of food components in the development and the function of the immune system. Studies in mice have already shown that dietary proteins are critical elements for the developmental shift of the immature neonatal immune profile into a fully developed immune system. The immunological effects of other food components (such as vitamins and lipids) will also be addressed. Most of the cells in the GALT are activated and local proinflammatory mediators are abundant. Regulatory elements are known to provide a delicate yet robust balance that keeps the gut homeostasis at check. Usually antigenic contact in the gut induces two major immune responses, oral tolerance and production of secretory IgA. However, under pathological conditions mucosal homeostasis is disturbed resulting in inflammatory reactions such as food hypersensitivity. Food allergy development depends on many factors such as genetic predisposition, biochemical features of allergens and a growing array of environmental elements. Neuroimmune interactions are also implicated in food allergy and they are examples of the high complexity of the phenomenon. Recent findings on the gut circuits triggered by food components will be reviewed to show that, far beyond their role as nutrients, they are critical players in the operation of immune system in health and disease

New Insights into the Immunological Changes in IL-10-Deficient Mice during the Course of Spontaneous Inflammation in the Gut Mucosa

IL-10 is a regulatory cytokine that plays a major role in the homeostasis of the gut and this is illustrated by the fact that IL-10−/− mice develop spontaneous colitis. In this study, IL-10−/− mice were analyzed for immunological changes during colitis development. We found a reduced frequency of regulatory T cells and higher frequency of activated T cells in the colon that precedes the macroscopic signs of the disease. Production of IL-17 and IFN-γ was higher in the colon. Colitis progression culminates with the reduction of regulatory T cells in the intestine. Frequency of B1 cells and the secretory IgA production were both elevated. Despite these alterations, 16-week-old IL-10−/− mice could be rendered tolerant by a continuous feeding protocol. Our study provides detailed analysis of changes that precede colitis and it also suggests that oral tolerance could be used to design novel alternative therapies for the disease.Peer Reviewe

Hsp65-Producing Lactococcus lactis Prevents Inflammatory Intestinal Disease in Mice by IL-10- and TLR2-Dependent Pathways

Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria. Using an IBD mouse model, we showed that oral pretreatment with genetically modified Lactococcus lactis that produces and releases Mycobacterium Hsp65, completely prevented DSS-induced colitis in C57BL/6 mice. Protection was associated with reduced pro-inflammatory cytokines, such as IFN-γ, IL-6, and TNF-α; increased IL-10 production in colonic tissue; and expansion of CD4+Foxp3+ and CD4+LAP+ regulatory T cells in spleen and mesenteric lymph nodes. This effect was dependent on IL-10 and toll-like receptor 2. Thus, this approach may open alternative options for long-term management of IBD

Interleukin-4 deficiency protects mice from acetaminophen-induced liver injury and inflammation by prevention of glutathione depletion

OBJECTIVE: Interleukin-4 (IL-4) is a multifunctional cytokine involved in many diseases such as autoimmune hepatitis and idiosyncratic drug reactions. However, its role in acetaminophen (APAP)-induced liver injury remains unclear. Our objective was to evaluate the contribution of IL-4 to the pathogenesis of APAP-induced liver injury. METHODS: Balb/C (WT) and IL-4 knockout (IL-4(-/-)) mice were orally overdosed with APAP. After 24 h, survival percentage, biochemical and morphological markers of liver injury, and tissue inflammation were assessed. RESULTS: IL-4(-/-) mice were protected from APAP toxicity. Intravital confocal microscopy, tissue histology and serum ALT levels showed significantly less liver injury and inflammation than in the WT group, which may explain the increased survival rate of IL-4(-/-) mice. In addition, IL-4(-/-) mice had decreased production of tumor necrosis factor α, CXCL1 and interleukin-1β in the liver, but not in a remote site such as the lungs. Hepatic macrophage activation was markedly reduced in IL-4-deficient mice. In addition, glutathione depletion-a primary cause of APAP-mediated injury-was significantly attenuated in IL-4(-/-) mice. CONCLUSIONS: Taken together, our data demonstrate that IL-4(-/-) mice are protected from APAP-induced liver injury due to reduced depletion of glutathione, which prevented liver damage and tissue inflammation.status: publishe

Anti-inflammatory effects of Lactococcus lactis NCDO 2118 during the remission period of chemically-induced colitis

Many probiotic bacteria have been described as a promising tool in the therapy of Inflammatory Bowel Diseases (IBD). Most of them belong to the Lactic Acid Bacteria (LAB) group, which makes part of our healthy microbiota. However, little is known about the effects of transiting dairy bacteria that make part of our diet, including Lactococcus lactis. In the present study, we analyzed the immune modulation effects of three L. lactis strains in vitro using intestinal epithelial cells and the effectiveness of a selected strain in a murine model of colitis. Only one strain, L. lactis NCDO 2118, was able to reduce the IL1-β-induced IL-8 secretion in Caco-2 cells, suggesting a potential anti-inflammatory effect of this strain. In vivo, L. lactis NCDO 2118 was administered for 4 days to C57BL/6 mice during a remission period between a first and second course of colitis induced by dextran sulfate sodium. This resulted in a milder form of recurrent colitis than observed in mice administered medium during this same period. This protective effect was not attributable to changes in secretory IgA, however NCDO 2118 administration was associated with early increase in IL-6 production and by the maintenance of IL-10 in colonic tissue. Mice fed with L. lactis NCDO 2118 increased the number of regulatory CD4+ T cells bearing surface TGF-β in the form of latency-associated protein in mesenteric lymph node and spleen. The results of this study allowed us to identify a new probiotic strain that may be used in the treatment of IBD as well as some of the mechanism involved in its anti-inflammatory effect. Fil: Diniz Luerce, Tessália. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Gomes Santos, Ana Cristina. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Santos Rochat, Clarissa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Garcias Moreira, Thais. Universidade Federal de Minas Gerais. Faculdade de Farmácia. Departamento de Ciência de Alimentos.; BrasilFil: Nogueira Cruz, Déborah. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Lemos, Luísa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Sousa, Adna Luciana. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Bastos Pereira, Vanessa. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: de Azevedo, Marcela. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Moraes, Kátia. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Carmona Cara, Denise. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia; BrasilFil: Leblanc, Jean Guy Joseph. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Tucumán. Centro de Referencia para Lactobacilos (i); ArgentinaFil: Azevedo, Vasco. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; BrasilFil: Caetano Faria, Ana Maria. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Bioquímica e Imunologia; BrasilFil: Miyoshi, Anderson. Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Biologia Geral; Brasi