PMID- 28799230 OWN - NLM STAT- MEDLINE DCOM- 20181109 LR - 20240313 IS - 1521-4141 (Electronic) IS - 0014-2980 (Print) IS - 0014-2980 (Linking) VI - 48 IP - 1 DP - 2018 Jan TI - Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. PG - 180-193 LID - 10.1002/eji.201747024 [doi] 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. CI - (c) 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. FAU - Cirauqui, Cristina AU - Cirauqui C AD - Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain. FAU - Benito-Villalvilla, Cristina AU - Benito-Villalvilla C AD - Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain. FAU - Sanchez-Ramon, Silvia AU - Sanchez-Ramon S AD - Department of Immunology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. AD - Dpt. of Microbiology I-Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. FAU - Sirvent, Sofia AU - Sirvent S AD - Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain. FAU - Diez-Rivero, Carmen M AU - Diez-Rivero CM AD - Inmunotek S.L., Madrid, Spain. FAU - Conejero, Laura AU - Conejero L AD - Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. FAU - Brandi, Paola AU - Brandi P AD - Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. FAU - Hernandez-Cillero, Lourdes AU - Hernandez-Cillero L AD - Department of Immunology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. AD - Genomics and Microarray Laboratory, Department of Medical Oncology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. FAU - Ochoa, Juliana Lucia AU - Ochoa JL AD - Department of Immunology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. FAU - Perez-Villamil, Beatriz AU - Perez-Villamil B AD - Genomics and Microarray Laboratory, Department of Medical Oncology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. FAU - Sancho, David AU - Sancho D AD - Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain. FAU - Subiza, Jose Luis AU - Subiza JL AD - Department of Immunology, Instituto de Investigacion Sanitaria, Hospital Clinico San Carlos (IdISSC), Madrid, Spain. AD - Dpt. of Microbiology I-Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. AD - Inmunotek S.L., Madrid, Spain. FAU - Palomares, Oscar AU - Palomares O AUID- ORCID: 0000-0003-4516-0369 AD - Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170914 PL - Germany TA - Eur J Immunol JT - European journal of immunology JID - 1273201 RN - 0 (Bacterial Vaccines) RN - 0 (IL10 protein, human) RN - 0 (MYD88 protein, human) RN - 0 (Myeloid Differentiation Factor 88) RN - 130068-27-8 (Interleukin-10) RN - EC 2.7.11.1 (RIPK2 protein, human) RN - EC 2.7.11.1 (Receptor-Interacting Protein Serine-Threonine Kinase 2) SB - IM MH - Adult MH - Aged MH - Animals MH - Bacterial Vaccines/*immunology MH - Cells, Cultured MH - Dendritic Cells/*immunology MH - Female MH - Humans MH - Interleukin-10/*immunology MH - Male MH - Mice MH - Mice, Inbred BALB C MH - Middle Aged MH - Myeloid Differentiation Factor 88/*metabolism MH - Receptor-Interacting Protein Serine-Threonine Kinase 2/*metabolism MH - Respiratory Tract Infections/immunology/microbiology/*prevention & control MH - Signal Transduction/immunology MH - Th1 Cells/*immunology MH - Th17 Cells/*immunology PMC - PMC5813220 OTO - NOTNLM OT - Dendritic cells (DCs) OT - IL-10-producing T cells OT - Recurrent respiratory tract infections (RRTIs) OT - Th1/Th17 cells OT - Whole heat-inactivated polybacterial vaccines EDAT- 2017/08/12 06:00 MHDA- 2018/11/10 06:00 PMCR- 2018/02/15 CRDT- 2017/08/12 06:00 PHST- 2017/03/01 00:00 [received] PHST- 2017/07/14 00:00 [revised] PHST- 2017/08/08 00:00 [accepted] PHST- 2017/08/12 06:00 [pubmed] PHST- 2018/11/10 06:00 [medline] PHST- 2017/08/12 06:00 [entrez] PHST- 2018/02/15 00:00 [pmc-release] AID - EJI4107 [pii] AID - 10.1002/eji.201747024 [doi] PST - ppublish SO - Eur J Immunol. 2018 Jan;48(1):180-193. doi: 10.1002/eji.201747024. Epub 2017 Sep 14.