RT Journal Article T1 Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways A1 Cirauqui, Cristina A1 Benito Villalvilla, Cristina A1 Sánchez Ramón, Silvia María A1 Sirvent, Sofía A1 Diez Rivero, Carmen María A1 Conejero, Laura A1 Brandi, Paola A1 Hernández Cillero, Lourdes A1 Ochoa, Juliana Lucía A1 Pérez Villamil, Beatriz A1 Sancho, David A1 Subiza Garrido-Lestache, José Luis A1 Palomares Gracia, Óscar AB Recurrent 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 gene-88 (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. PB Wiley SN 0014-2980 YR 2018 FD 2018 LK https://hdl.handle.net/20.500.14352/95326 UL https://hdl.handle.net/20.500.14352/95326 LA eng NO Cirauqui C, Benito-Villalvilla C, Sánchez-Ramón S, Sirvent S, Diez-Rivero CM, Conejero L, Brandi P, Hernández-Cillero L, Ochoa JL, Pérez-Villamil B, Sancho D, Subiza JL, Palomares O. Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. Eur J Immunol. 2018 Jan;48(1):180-193. doi: 10.1002/eji.201747024 NO Ministerio de Economía, Comercio y Empresa (España) NO Comisión Europea NO Ministerio de Ciencia, Innovación y Universidades (España) DS Docta Complutense RD 30 sept 2024