Activation of IL-10+ B cells: A novel immunomodulatory mechanism for therapeutic bacterial suspensions

Abstract

Objectives: Bacterial components are used to improve immune responses in patients with respiratory infections. Pharmacological formulations of bacterial components include a mixture of bacterial antigens, some of which are complete inactivated bacteria, that is, named bacterial suspensions; while others are fragments of bacteria, which are presented as bacterial lysates. Although bacterial lysates have been broadly used as immune-stimulators, the biological support for the therapeutic effectiveness of bacterial suspension has not yet been studied. Thus, the aim of our study was to investigate the immunological activity induced by bacterial suspension. Methods: This work was an exploratory translational study. Peripheral blood mononuclear cells were obtained from healthy donors and cultured in time–dose dependent assays with a commercial bacterial suspension. Flow cytometry was used for phenotypic analysis and for determining soluble cytokines in culture supernatants. Results: We observed that bacterial suspension activates B cells in a dose-dependent manner. Peripheral blood mononuclear cells were able to secrete IL-6 and IL-10 after 24 h of bacterial suspension stimulation. TLR2 expression was observed mainly on CD19+ CD38Lo B cells after 72 h of culture; remarkably, most of the TLR2+ CD19+ cells were also IL-10+. Conclusion: Our findings suggest that bacterial suspension induces the activation of B cell subsets as well as the secretion of IL-6 and IL-10. Expression of TLR2 on CD19+ cells could act as an activation loop of IL-10+ B regulatory cells. The clinical implications of these findings are discussed at the end of this article.

Immune Response against Adenovirus in Acute Upper Respiratory Tract Infections in Immunocompetent Children

“…In another study, the profile exhibited during the acute phase of adenovirus-induced AURTIs, with significant elevation of both IL-6 and IL-10, resembles the one of peripheral mononuclear cells stimulated with bacterial lysates; the production of these mediators seemed to be driven by B cells through TLR-2 pathway [ 51 ]. Immune stimulation of B cells in vitro with bacterial debrides elicits a response in the supernatant similar to what we encountered in the serum of our population during the acute phase, when IL-6, IL-10, and B cells were higher than during convalescence [ 51 ]. Although bacterial and viral infections have showed to differ significantly in terms of serum markers, taken together, previous experiences and our study, enforce the long-time experience that depicts HAdV as a viral agent with a bacterial “signature”.…”

“…The subsets of B cells that are the actual source of these cytokines have to be investigated, and the contribution of the single blood cell subpopulation is beyond the purpose of this work [ 51 ].…”