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Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways.
Eur J Immunol. 2018 01; 48(1):180-193.EJ

Abstract

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.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.Department of Immunology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Dpt. of Microbiology I-Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain.Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.Inmunotek S.L., Madrid, Spain.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.Department of Immunology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Genomics and Microarray Laboratory, Department of Medical Oncology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain.Department of Immunology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain.Genomics and Microarray Laboratory, Department of Medical Oncology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain.Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain.Department of Immunology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain. Dpt. of Microbiology I-Immunology, School of Medicine, Complutense University of Madrid, Madrid, Spain. Inmunotek S.L., Madrid, Spain.Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28799230

Citation

Cirauqui, Cristina, et al. "Human Dendritic Cells Activated With MV130 Induce Th1, Th17 and IL-10 Responses Via RIPK2 and MyD88 Signalling Pathways." European Journal of Immunology, vol. 48, no. 1, 2018, pp. 180-193.
Cirauqui C, Benito-Villalvilla C, Sánchez-Ramón S, et al. Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. Eur J Immunol. 2018;48(1):180-193.
Cirauqui, C., Benito-Villalvilla, C., Sánchez-Ramón, S., Sirvent, S., Diez-Rivero, C. M., Conejero, L., Brandi, P., Hernández-Cillero, L., Ochoa, J. L., Pérez-Villamil, B., Sancho, D., Subiza, J. L., & Palomares, O. (2018). Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. European Journal of Immunology, 48(1), 180-193. https://doi.org/10.1002/eji.201747024
Cirauqui C, et al. Human Dendritic Cells Activated With MV130 Induce Th1, Th17 and IL-10 Responses Via RIPK2 and MyD88 Signalling Pathways. Eur J Immunol. 2018;48(1):180-193. PubMed PMID: 28799230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways. AU - Cirauqui,Cristina, AU - Benito-Villalvilla,Cristina, AU - Sánchez-Ramón,Silvia, AU - Sirvent,Sofía, AU - Diez-Rivero,Carmen M, AU - Conejero,Laura, AU - Brandi,Paola, AU - Hernández-Cillero,Lourdes, AU - Ochoa,Juliana Lucía, AU - Pérez-Villamil,Beatriz, AU - Sancho,David, AU - Subiza,José Luis, AU - Palomares,Oscar, Y1 - 2017/09/14/ PY - 2017/03/01/received PY - 2017/07/14/revised PY - 2017/08/08/accepted PY - 2017/8/12/pubmed PY - 2018/11/10/medline PY - 2017/8/12/entrez KW - Dendritic cells (DCs) KW - IL-10-producing T cells KW - Recurrent respiratory tract infections (RRTIs) KW - Th1/Th17 cells KW - Whole heat-inactivated polybacterial vaccines SP - 180 EP - 193 JF - European journal of immunology JO - Eur J Immunol VL - 48 IS - 1 N2 - 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. SN - 1521-4141 UR - https://www.unboundmedicine.com/medline/citation/28799230/Human_dendritic_cells_activated_with_MV130_induce_Th1_Th17_and_IL_10_responses_via_RIPK2_and_MyD88_signalling_pathways_ L2 - https://doi.org/10.1002/eji.201747024 DB - PRIME DP - Unbound Medicine ER -