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.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
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 Odoi
10.1002/eji.201747024subject
Has Abstractpub_date
2018-01-01 00:00:00pages
180-193issue
1eissn
0014-2980issn
1521-4141journal_volume
48pub_type
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