MV140, a sublingual polyvalent bacterial preparation to treat recurrent urinary tract infections, licenses human dendritic cells for generating Th1, Th17, and IL-10 responses via Syk and MyD88
| Autor: | Oscar Palomares, M Casanovas, José Luis Subiza, Cristina Cirauqui, Cristina Benito-Villalvilla, Carmen M. Diez-Rivero |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.drug_class Immunology Antibiotics Administration Sublingual Syk Inflammation Biology Mice 03 medical and health sciences Immune system Recurrence Immunity medicine Animals Humans Syk Kinase Immunology and Allergy Cells Cultured Mice Inbred BALB C Dendritic Cells Th1 Cells Interleukin-10 Interleukin 10 030104 developmental biology Mucosal immunology Bacterial Vaccines Myeloid Differentiation Factor 88 Urinary Tract Infections Th17 Cells Immunization Signal transduction medicine.symptom Signal Transduction |
| Zdroj: | Mucosal Immunology. 10:924-935 |
| ISSN: | 1933-0219 |
| DOI: | 10.1038/mi.2016.112 |
| Popis: | Recurrent urinary tract infections (RUTIs) are one of the most common bacterial infectious diseases, especially in women. Antibiotics remain the mainstay of treatment, but their overuse is associated with antibiotic-resistant infections and deleterious effects in the microbiota. Therefore, alternative approaches are fully demanded. Sublingual immunization with MV140 (Uromune), a polyvalent bacterial preparation (PBP) of whole heat-inactivated bacteria, demonstrated clinical efficacy for the treatment of RUTIs, but the involved immunological mechanisms remain unknown. Herein, we demonstrated that MV140 endorses human dendritic cells (DCs) with the capacity to generate Th1/Th17 and IL-10-producing T cells by mechanisms depending on spleen tyrosine kinase (Syk)- and myeloid differentiation primary response gene 88 (MyD88)-mediated pathways. MV140-induced activation of nuclear factor κB (NF-κB) and p38 in human DCs is essential for the generated Th1/Th17 and IL-10 immune responses whereas c-Jun N-terminal Kinase (JNK) and extracellular-signal regulated kinase (ERK) contribute to Th1 and IL-10 responses, respectively. Sublingual immunization of BALB/c mice with MV140 also induces potent systemic Th1/Th17 and IL-10 responses in vivo. We uncover immunological mechanisms underlying the way of action of MV140, which might well also contribute to understand the rational use of specific PBPs in other clinical conditions with potential high risk of recurrent infections. |
| Databáze: | OpenAIRE |
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