Examinando por Autor "Vargas, Pablo"

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    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.
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    Immunization with antigen-pulsed dendritic cells significantly improves the immune response to weak self-antigens
    (Elsevier GmbH, 2006-02) Vargas, Pablo; Cortés, Claudio; Vargas, Leonardo; Rosemblatt, Mario; Bono, María Rosa
    Dendritic cells (DCs) are the only professional antigen-presenting cells endowed with the ability to stimulate naïve T cells and initiate a primary immune response. For this reason, DC-based immunization has been shown to be highly effective in eliciting CTL responses to viruses and tumor-associated antigens. Here we report on the use of DC immunization to enhance the B cell-mediated humoral immune response to highly conserved proteins and the application of this approach to the generation of monoclonal antibodies (mAbs) against these proteins. To illustrate the technique we describe the production of mAbs to class II transactivator (CIITA), the major histocompatibility complex (MHC) CIITA, a difficult immunogen owing to its high degree of identity among species. We show that mice immunized with a combination of an intravenous injection of DCs pulsed with recombinant fragments of CIITA followed by intraperitoneal injection of the antigen in incomplete Freund's adjuvant induced a detectable antibody response against CIITA, while sera from mice immunized using the traditional method (i.e. intraperitoneal immunization with 50 μg of protein in complete Freund's adjuvant) gave an almost undetectable response. Furthermore, a total of four fusion experiments demonstrate that immunization with Ag-pulsed DCs is necessary for the efficient generation of hybridomas and a good yield of mAbs specific for the recombinant and the native endogenous CIITA protein. Conversely, four independent fusions carried out with splenocytes from mice immunized using the traditional method failed to produce anti-CIITA hybridomas. We propose that immunization with antigen-loaded DCs should be the method of preference when attempting to raise mAbs against weak self-immunogens. © 2005 Elsevier GmbH. All rights reserved.