An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity

Pasantías de investigación para alumnos que cursan el último año de la escuela secundaria

El objetivo principal es estimular en los alumnos el concepto de posibilidad de realizar una carrera biomédica, basado simple y necesariamente en la voluntad y el esfuerzo, proponiendo el acercamiento a una unidad académica y a un grupo de docentes-investigadores en un plano personalizado, con un lenguaje accesible y en una condición de contención que permita que el alumno confronte su propia realidad con un proyecto universitario al alcance de su entorno económico social.Facultad de Ciencias Médica

Depletion of Dendritic Cells Enhances Innate Anti-Bacterial Host Defense through Modulation of Phagocyte Homeostasis

Dendritic cells (DCs) as professional antigen-presenting cells play an important role in the initiation and modulation of the adaptive immune response. However, their role in the innate immune response against bacterial infections is not completely defined. Here we have analyzed the role of DCs and their impact on the innate anti-bacterial host defense in an experimental infection model of Yersinia enterocolitica (Ye). We used CD11c-diphtheria toxin (DT) mice to deplete DCs prior to severe infection with Ye. DC depletion significantly increased animal survival after Ye infection. The bacterial load in the spleen of DC-depleted mice was significantly lower than that of control mice throughout the infection. DC depletion was accompanied by an increase in the serum levels of CXCL1, G-CSF, IL-1α, and CCL2 and an increase in the numbers of splenic phagocytes. Functionally, splenocytes from DC-depleted mice exhibited an increased bacterial killing capacity compared to splenocytes from control mice. Cellular studies further showed that this was due to an increased production of reactive oxygen species (ROS) by neutrophils. Adoptive transfer of neutrophils from DC-depleted mice into control mice prior to Ye infection reduced the bacterial load to the level of Ye-infected DC-depleted mice, suggesting that the increased number of phagocytes with additional ROS production account for the decreased bacterial load. Furthermore, after incubation with serum from DC-depleted mice splenocytes from control mice increased their bacterial killing capacity, most likely due to enhanced ROS production by neutrophils, indicating that serum factors from DC-depleted mice account for this effect. In summary, we could show that DC depletion triggers phagocyte accumulation in the spleen and enhances their anti-bacterial killing capacity upon bacterial infection

PAC research in Biology

Abstract: In this paper possible applications of Perturbed Angular Correlations (PAC) technique in Biology are considered. Previous PAC experiments in biology are globally analyzed. All the work that appears in the literature has been organized in a few lines of research, just to make the analysis and discussion easy. The commonly used radioactive probes are listed and the experimental difficulties are analyzed. We also report applications of 181 Hf and 111 In isotopes in lifesciences other than their use in PAC. The possibility of extending these studies using the PAC technique is discussed

Glutathione Complexed Fe–S Centers

Glutathione (γ-glutamyl-cysteinyl-glycine, GSH) is a major thiol-containing peptide with cellular levels of up to 10 mM. Several recent reports have demonstrated glutaredoxins (Grx) to form [Fe₂S₂] cluster-bridged dimers, where glutathione provides two exogenous thiol ligands, and have implicated such species in cellular iron sulfur cluster biosynthesis. We report the finding that glutathione alone can coordinate and stabilize an [Fe₂S₂] cluster under physiological conditions, with optical, redox, Mössbauer, and NMR characteristics that are consistent with a [Fe₂S₂]­(GS)₄ composition. The Fe–S assembly protein ISU catalyzes formation of [Fe₂S₂]­(GS)₄ from iron and sulfide ions in the presence of glutathione, and the [Fe₂S₂] core undergoes reversible exchange between apo ISU and free glutathione