Human dendritic cells activated with MV130 induce Th1, Th17 and IL-10 responses via RIPK2 and MyD88 signalling pathways.

Autor: Cirauqui C; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain., Benito-Villalvilla C; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain., Sánchez-Ramón S; 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., Sirvent S; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain., Diez-Rivero CM; Inmunotek S.L., Madrid, Spain., Conejero L; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Brandi P; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Hernández-Cillero L; 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., Ochoa JL; Department of Immunology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain., Pérez-Villamil B; Genomics and Microarray Laboratory, Department of Medical Oncology, Instituto de Investigación Sanitaria, Hospital Clínico San Carlos (IdISSC), Madrid, Spain., Sancho D; Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid, Spain., Subiza JL; 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., Palomares O; Department of Biochemistry and Molecular Biology, School of Chemistry, Complutense University, Madrid, Spain.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2018 Jan; Vol. 48 (1), pp. 180-193. Date of Electronic Publication: 2017 Sep 14.
DOI: 10.1002/eji.201747024
Abstrakt: 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.
(© 2017 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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