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dc.contributor.authorCirauqui, Cristina
dc.contributor.authorBenito-Villalvilla, Cristina
dc.contributor.authorSanchez-Ramon, Silvia
dc.contributor.authorSirvent, Sofia
dc.contributor.authorDiez-Rivero, Carmen M.
dc.contributor.authorConejero, Laura 
dc.contributor.authorBrandi, Paola 
dc.contributor.authorHernandez-Cillero, Lourdes
dc.contributor.authorOchoa, Juliana Lucia
dc.contributor.authorPerez-Villamil, Beatriz
dc.contributor.authorSancho, David 
dc.contributor.authorLuis Subiza, Jose
dc.contributor.authorPalomares, Óscar
dc.identifier.citationEur J Immunol. 2018; 48(1):180-193
dc.description.abstractRecurrent respiratory tract infections (RRTIs) are the first leading cause of community-and nosocomial-acquired infections. Antibiotics remain the mainstay of treatment, enhancing the potential to develop antibiotic resistances. Therefore, the development of new alternative approaches to prevent and treat RRTIs is highly demanded. Daily sublingual administration of the whole heat-inactivated polybacterial preparation (PBP) MV130 significantly reduced the rate of respiratory infections in RRTIs patients, however, the immunological mechanisms of action remain unknown. Herein, we study the capacity of MV130 to immunomodulate the function of human dendritic cells (DCs) as a potential mechanism that contribute to the clinical benefits. We demonstrate that DCs from RRTIs patients and healthy controls display similar ex vivo immunological responses to MV130. By combining systems biology and functional immunological approaches we show that MV130 promotes the generation of Th1/Th17 responses via receptor-interacting serine/threonine-protein kinase-2 (RIPK2)-and myeloid-differentiation primary-response gene88 (MyD88)-mediated signalling pathways under the control of IL-10. In vivo BALB/c mice sublingually immunized with MV130 display potent systemic Th1/Th17 and IL-10 responses against related and unrelated antigens. We elucidate immunological mechanisms underlying the potential way of action of MV130, which might help to design alternative treatments in other clinical conditions with high risk of recurrent infections.
dc.description.sponsorshipThis work was supported by grant IPT-2012-0639-090000 from INNPACTO and MINECO, Spain to Inmunotek S.L. The authors' laboratories are supported by grants SAF2014-52706-R to O.P. from MINECO, Spain, and SAF2016-79040R to D.S. from MINECO and European Fund for Regional Development, Spain. O.P. is a Ramon y Cajal Scholar funded by MINECO and the European Social Fund. L.C. is a recipient of a European Respiratory Society Fellowship (RESPIRE2-2013-3708). We thank to Juan Lopez-Relano and Sarai Martinez-Cano for excellent technical assistance with mice experiments.
dc.relation.isversionofPublisher's version
dc.subjectDendritic cells (DCs)
dc.subjectIL-10-producing T cells
dc.subjectRecurrent respiratory tract infections (RRTIs)
dc.subjectTh1/Th17 cells
dc.subjectWhole heat-inactivated polybacterial vaccines
dc.titleHuman dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways
dc.rights.licenseAtribución 4.0 Internacional*
dc.contributor.funderMinisterio de Economía, Industria y Competitividad (España)
dc.contributor.funderEuropean Regional Development Fund 
dc.contributor.funderEuropean Respiratory Society
dc.identifier.journalEuropean Journal of Immunology
dc.repisalud.orgCNICCNIC::Grupos de investigación::Inmunobiología

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