Examinando por Autor "Michea, Paula"

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    Cyclosporin A-treated Dendritic Cells may affect the outcome of organ transplantation by decreasing CD4+CD25+ regulatory T cell proliferation
    (Sociedad de Biología de Chile, 2010) Pino, Karina; Michea, Paula; Sauma, Daniela; Alba, Andrea; Morales, Jorge; Bono Merino, María Rosa; Fierro, Alberto; Rosemblatt, Mario
    One of the mechanisms for generation of tolerance involves immature dendritic cells (DCs) and a subpopulation of regulatory CD4+ CD25+ T lymphocytes (TREG). The purpose of this work was to analyze how Cyclosporine A (CsA), a widely used immunosuppressive drug, may affect TREG proliferation. Purified and activated murine DCs obtained from bone marrow precursors differentiated with rGMCSF were co-cultured with purified CFSE-labeled TREG from OTII mice, and their phenotype and proliferation analyzed by flow cytometry. Our data indicate that DCs differentiated in the presence of CsA show an altered phenotype, with a lower expression of MHC-II and a lower activating capacity. Additionally, these CsA-treated DCs show decreased production of IL-2 and IL-12 and increased IL-10 secretion when stimulated with LPS, indicating an effect on the polarization of the immune response. Interestingly, CsA-treated DCs show an anti-tolerogenic effect since they reduce the proliferation of TREG cells from 72 to 47%. Further inhibition to a 24% of TREG proliferation was obtained as a direct effect of CsA on TREG. In conclusion, the anti-tolerogenic effect of CsA should be considered in the planning of immunosuppression in the context of clinical transplantation.
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    Ítem
    Epithelial control of the human pDC response to extracellular bacteria
    (2013-04) Michea, Paula; Vargas, Pablo; Donnadieu, Marie-Hélène; Rosemblatt, Mario; Bono, María Rosa; Duménil, Guillaume; Soumelis, Vassili
    Plasmacytoid pre-dendritic cells (pDCs) are specialized in responding to nucleic acids, and link innate with adaptive immunity. Although the response of pDCs to viruses is well established, whether pDCs can respond to extracellular bacteria remains controversial. Here, we demonstrate that extracellular bacteria such as Neisseria meningitidis, Haemophilus influenzae, and Staphylococcus aureus activate pDCs to produce IFN-α, TNF-α, IL-6, and to upregulate CD86 expression. We observed that pDCs were present within tonsillar crypts and oro-nasopharyngeal epithelium, where they may contact extracellular bacteria, in situ. Tonsil epithelium-conditioned supernatants inhibited IFN-α, TNF-α, and IL-6 triggered by the direct contact of N. meningitidis or S. aureus with pDCs. However, pDC priming of naive T cells was not affected, suggesting that tonsil epithelium micro-environment limits local inflammation while preserving adaptive immunity in response to extracellular bacteria. Our results reveal an important and novel function of pDCs in the initiation of the mucosal innate and adaptive immunity to extracellular bacteria. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.