Abstract
BackgroundLactic acid bacteria are commensal members of the gut microbiota and are postulated to promote host health. Secreted factors and cell surface components from Lactobacillus species have been shown to modulate the host immune system. However, the precise role of L. reuteri secreted factors and surface proteins in influencing dendritic cells (DCs) remains uncharacterized.HypothesisWe hypothesize that L. reuteri secreted factors will promote DC maturation, skewing cells toward an anti‐inflammatory phenotype. In acute colitis, we speculate that L. reuteri promotes IL‐10 and dampens pro‐inflammatory cytokine production, thereby improving colitis.Methods & ResultsMouse bone marrow‐derived DCs were differentiated into immature dendritic cells (iDCs) via IL‐4 and GM‐CSF stimulation. iDCs exposed to L. reuteri secreted factors or UV‐irradiated bacteria exhibited greater expression of DC maturation markers CD83 and CD86 by flow cytometry. Additionally, L. reuteri stimulated DCs exhibited phenotypic maturation as denoted by cytokine production, including anti‐inflammatory IL‐10. Using mouse colonic organoids, we found that the microinjection of L. reuteri secreted metabolites and UV‐irradiated bacteria was able to promote IL‐10 production by DCs, indicating potential epithelial‐immune cross‐talk. In a TNBS‐model of acute colitis, L. reuteri administration significantly improved histological scoring, colonic cytokine mRNA, serum cytokines, and bolstered IL‐10 production.ConclusionsOverall these data demonstrate that both L. reuteri secreted factors and its bacterial components are able to promote DC maturation. This work points to the specific role of L. reuteri in modulating intestinal DCs.New & Noteworthy Lactobacillus reuteri colonizes the mammalian gastrointestinal tract and exerts beneficial effects on host health. However, the mechanisms behind these effects have not been fully explored. In this article, we identified that L. reuteri ATTC PTA 6475 metabolites and surface components promote dendritic cell maturation and IL‐10 production. In acute colitis, we also demonstrate that L. reuteri can promote IL‐10 and suppress inflammation. These findings may represent a crucial mechanism for maintaining intestinal immune homeostasis.
Highlights
Dendritic cells (DCs) are migratory phagocytic cells that act as the gatekeepers of the immune system (Cella et al, 1997; Hammer & Ma, 2013; Kelsall et al, 2002; Kelsall & Strober, 1997; Mowat et al, 2003)
Among the cytokines produced by dendritic cells (DC), interleukin 10 (IL10) is a key anti-inflammatory cytokine that aids in preventing chronic inflammation and tissue damage (Schulke, 2018)
We found that the direct application of L. reuteri conditioned media, bacteria, and LPS stimulated the substantial secretion of IL-10, with the highest levels observed with LPS and L. reuteri bacteria (Figure 4B)
Summary
These effects have not been fully explored. We demonstrate that L. reuteri can promote IL-10 and suppress inflammation. These findings may represent a crucial mechanism for maintaining intestinal immune homeostasis
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