Abstract
Lactobacilli are widely used as probiotics with beneficial effects on infection-associated diarrhea, but also used in clinical trials of e.g., necrotizing enterocolitis and inflammatory bowel diseases. The possibility of using probiotic metabolic products, so-called postbiotics, is desirable as it could prevent possible side effects of live bacteria in individuals with a disturbed gut epithelial barrier. Here, we studied how Lactobacillus reuteri DSM 17938 cell-free supernatant (L. reuteri-CFS) influenced retinoic acid (RA)-driven mucosal-like dendritic cells (DC) and their subsequent effect on T regulatory cells (Treg) in vitro. RA clearly imprinted a mucosal-like DC phenotype with higher IL10 production, increased CD103 and CD1d expression, and a downregulated mRNA expression of several inflammatory-associated genes (NFκB1, RELB, and TNF). Treatment with L. reuteri-CFS further influenced the tolerogenic phenotype of RA-DC by downregulating most genes involved in antigen uptake, antigen presentation, and signal transduction as well as several chemokine receptors, while upregulating IL10 production. L. reuteri-CFS also augmented CCR7 expression on RA-DC. In cocultures, RA-DC increased IL10 and FOXP3 expression in Treg, but pre-treatment with L. reuteri-CFS did not further influence the Treg phenotype. In conclusion, L. reuteri-CFS modulates the phenotype and function of mucosal-like DC, implicating its potential application as postbiotic.
Highlights
The mucosal immune system in the gut is continuously exposed to innocuous dietary antigens and commensal microbes
Gene expression of molecules associated with transmigration and gut homing like ICAM1 and ICAM2 were upregulated in retinoic acid (RA)-dendritic cells (DC) together with some chemokines such as CCL2, CCL5, and CCL7
To elucidate whether postbiotics derived from L. reuteri DSM 17938 could influence the functional phenotype and secretory profile of RA-DC and monocyte derived (Mo-)DC, we investigated the expression of DC-associated genes post-stimulation with L. reuteri-cell-free supernatant (CFS)
Summary
The mucosal immune system in the gut is continuously exposed to innocuous dietary antigens and commensal microbes. Apart from its well-known effects on gut homeostasis and metabolic functions, this local microenvironment plays a major role in shaping the response of immune cells in their specialized tissue-associated functions; for instance intestinal epithelial cells influence the gut dendritic cells (DC) response, which subsequently influence T cell responses. Factors such as thymic stromal lymphopoietin and indoleamine 2,3-dioxygenase produced by epithelial cells confer a tolerogenic phenotype on DC [1]. Epithelial cells have been shown to metabolize vitamin A into retinoic acid (RA) [2]. RA has been shown to promote the migration of pre-DC, the precursor of CD103+ DC, to the small intestine [3] and to induce CD103+ expression in monocyte derived (Mo-) DC in vitro [4].
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