D1.98 - MV130 drives the differentiation of human monocytes into dendritic cells with antiallergic properties

Asthma is one of the most common chronic inflammatory diseases of the airways both in children and adults affecting around 400 million people worldwide. Asthma attacks or exacerbations are mainly triggered by viral infections and allergen exposition. MV130 is a whole-heat inactivated polyvalent bacterial vaccine that has demonstrated efficacy in preventing recurrent respiratory tract infections (RRTI) in adults and viral-induced bronchiolitis in children. We sought to investigate the potential capacity of MV130 to modulate the differentiation of human monocytes into dendritic cells (hmoDCs) and the underlying molecular mechanisms.

Monocytes isolated from healthy donors were differentiated into hmoDCs under conventional protocols in the absence or presence of MV130 (MV130-hmoDCs). These cells were stimulated with house dust mite extract (HDM) and costimulatory molecules and cytokine signature were analyzed by flow cytometry and ELISA, respectively. MV130-hmoDCs were cocultured with allogeneic naïve CD4+ T cells to assess T cell responses. Metabolic and epigenetic rewiring in MV130-hmoDCs was determined by using qPCR, miRNA analysis, chromatin immunoprecipitation and metabolic studies (glucose consumption, lactate production, Warburg effect and mitochondrial membrane potential).

Differentiation of monocytes in the presence of MV130 resulted in the generation of hmoDCs able to produce higher IL-12 and lower pro-inflammatory cytokines than conventional hmoDCs, thus leading to higher IL-10/IL-1β, IL-10/TNF-α and IL-10/IL-6 ratios. MV130-hmoDCs display enhanced capacity to polarize naïve CD4+ T cells towards Th1 and FOXP3+ regulatory T cells. Mechanistically, MV130-hmoDCs showed increased glycolysis, lactate production, Warburg effect and mitochondrial oxidative phosphorylation. The reported metabolic reprogramming was accompanied by epigenetic rewiring, mainly characterized by increased levels of miRNA-155 and miRNA-146a/b.

MV130 favors the differentiation of human monocytes into DCs with antiallergic properties able to polarize Th1 and regulatory T cells by mechanisms partially depending on metabolic and epigenetic reprogramming. Our data might contribute to pave the way for MV130 as a potential strategy for the prevention and treatment of allergic asthma.