Generation of tolerogenic dendritic cells using Lactobacillus rhamnosus and Lactobacillus delbrueckii as tolerogenic probiotics

Abstract

Systemic lupus erythematosus (SLE) concurs with excessive uncontrolled inflammatory immune responses that lead to the loss of immune tolerance. Dendritic cells (DCs) are important and determinant immune cells that regulate immune responses. Tolerogenic DCs with regulatory markers and cytokines could induce regulatory immune cells and responses. Tolerogenic probiotics are capable of producing regulatory DCs from monocytes in in vitro conditions. The purpose of this study was to evaluate the effect of Lactobacillus delbrueckii and Lactobacillus rhamnosus on the production of DCs in an in vitro condition. Peripheral blood mononuclear cells were isolated from the healthy and SLE donors. Monocytes were cultured with optimized concentrations of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4) to produce immature DCs (IDCs). An IDC uptake assay was performed, and IDCs of healthy and SLE donors were divided into three subgroups following 48 hours of treatment with GM-CSF and IL-4, along with L. delbrueckii, L. rhamnosus, and mixed probiotics for the production of tolerogenic DCs. The surface expression of Human Leukocyte Antigen-antigen D Related (HLA-DR), CD86, CD80, CD83, CD1a, and CD14 was analyzed using flow cytometry, and the gene expression levels of indoleamine 2,3-dioxygenase (IDO), IL-10, and IL-12 were measured using real-time polymerase chain reaction. We observed significantly reduced expression of costimulatory molecules and other surface markers in the probiotic-induced mature DCs (MDCs) in both healthy and SLE donor groups in comparison with lipopolysaccharide (LPS)-induced MDCs. In addition, the expression of IDO and IL-10 increased, whereas IL-12 decreased significantly in probiotic-induced MDCs compared with LPS-induced MDCs. IDCs and especially mature tolerogenic DC of SLE patients highly expressed IDO. The results of the current study suggested that live probiotics could modify properties of DCs to modulatory cells, which might contribute to the induction of tolerance and renovation of immune hemostasis.

Probiotics in Autoimmune and Inflammatory Disorders

“…At this time, we are unaware of any randomized controlled trials of a probiotic for patients with lupus, but there is evidence that the gastrointestinal tract may be an avenue for disease modification. In vitro, probiotic lactobacilli when cultured with immature dendritic cells from lupus patients reduce the expression of costimulatory molecules and increase levels of interleukin-10 and indoleamine 2,3-dioxygenase (anti-inflammatory molecules), suggesting that they could promote immune tolerance [ 53 ]. A pilot study by Frech et al in a related autoimmune disorder, progressive systemic sclerosis, suggested that probiotics significantly improved esophageal reflux, distention and bloating, and total gastrointestinal symptom scales [ 54 ].…”

Probiotics with ameliorating effects on the severity of skin inflammation in psoriasis: Evidence from experimental and clinical studies

“…They have been frequently declared to impede IBD, decrease irritable bowel symptoms and atopic dermatitis, inhibit diarrhea, and moderate lactose intolerance (Nutrition, 2004). Such health benefits of probiotics are attributed to their modulatory effects on metabolic and physiologic parameters influenced by commensal microbiota, such as the function of gut barrier, maturation of immune system, amount of metabolic end‐products as substrates to epithelial cells or responsible for changing the luminal conditions, and enzymatic modification of bile acids (Esmaeili et al, 2018; Hooper, Midtvedt, & Gordon, 2002). In mechanism, probiotics can affect their host mainly through their bactericidal activity, competitive exclusion, and/or modulatory effect on immune system (Al‐Salami, Mikov, Caccetta, & Golocorbin‐Kon, 2012).…”

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