Browsing by Author "Contreras, Francisco J."

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    Aldosterone Promotes Autoimmune Damage by Enhancing Th17-Mediated Immunity
    (AMER ASSOC IMMUNOLOGISTS, 2010) Herrada, Andres A.; Contreras, Francisco J.; Marini, Natacha P.; Amador, Cristian A.; Gonzalez, Pablo A.; Cortes, Claudia M.; Riedel, Claudia A.; Carvajal, Cristian A.; Figueroa, Fernando; Michea, Luis F.; Fardella, Carlos E.; Kalergis, Alexis M.
    Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated by aldosterone. In this study we show that aldosterone augmented the activation of CD8(+) T cells in a DC-dependent fashion. Consistently, the mineralocorticoid receptor was expressed by DCs, which showed activation of MAPK pathway and secreted IL-6 and TGF-beta in response to aldosterone. In addition, DCs stimulated with aldosterone impose a Th17 phenotype to CD4(+) T cells, which have recently been associated with the promotion of inflammatory and autoimmune diseases. Accordingly, we observed that aldosterone enhances the progression of experimental autoimmune encephalomyelitis, an autoimmune disease promoted by Th17 cells. In addition, blockade of the mineralocorticoid receptor prevented all aldosterone effects on DCs and attenuated experimental autoimmune encephalomyelitis development in aldosterone-treated mice. Our data suggest that modulation of DC function by aldosterone enhances CD8(+) T cell activation and promotes Th17-polarized immune responses, which might contribute to the inflammatory damage leading to hypertension and cardiovascular disease. The Journal of Immunology, 2010, 184: 191-202.
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    Immune complex-induced enhancement of bacterial antigen presentation requires Fcγ Receptor III expression on dendritic cells
    (2007) Herrada, Andres A.; Contreras, Francisco J.; Tobar, Jaime A.; Pacheco, Rodrigo; Kalergis, Alexis M.
    Dendritic cells (DCs) are capable of initiating adaptive immune responses against infectious agents by presenting pathogen-derived antigens on MHC molecules to naive T cells. Because of their key role in priming adaptive immunity, it is expected that interfering with DC function would be advantageous to the pathogen. We have previously shown that Salmonella enterica, serovar Typhimurium (ST), is able to survive inside DCs and interfere with their function by avoiding activation of bacteria-specific T cells. In contrast, when ST is targeted to Fc gamma receptors on the DC surface, bacteria are degraded and their antigens presented to T cells. However, the specific Fc gamma receptor responsible of restoring presentation of antigens remains unknown. Here, we show that IgG-coated ST was targeted to lysosomes and degraded and its antigens presented on MHC molecules only when the low-affinity activating Fc gamma RIII was expressed on DCs. Fc gamma RIII-mediated enhancement of Ag presentation led to a robust activation of T cells specific for bacteria-expressed antigens. Laser confocal and electron microscopy analyses revealed that IgG-coated ST was rerouted to the lysosomal pathway through an Fc gamma RIII-dependent mechanism. PI-3K activity was required for this process, because specific inhibitors promoted the survival of IgG-coated ST inside DCs and prevented DCs from activating bacteria-specific T cells. Our data suggest that the DC capacity to efficiently activate T cells upon capturing IgG-coated virulent bacteria is mediated by Fc gamma RIII and requires PI-3K activity.