Immunomodulation and Generation of Tolerogenic Dendritic Cells by Probiotic Bacteria in Patients with Inflammatory Bowel Disease.

Shaghayegh Baradaran Ghavami,Maryam Farmani,Hamid Asadzadeh Aghdaei,Abbas Yadegar,Shabnam Shahrokh,Hedieh Balaii,Dario Sorrentino,Adil Shamim Mir,Masoumeh Azimirad,Mohammad Reza Zali

doi:10.3390/ijms21176266

Abstract

In inflammatory bowel diseases (IBD), the therapeutic benefit and mucosal healing from specific probiotics may relate to the modulation of dendritic cells (DCs). Herein, we assessed the immunomodulatory effects of four probiotic strains including Lactobacillus salivarius, Bifidobacterium bifidum, Bacillus coagulans and Bacillus subtilis natto on the expression of co-stimulatory molecules, cytokine production and gene expression of signal-transducing receptors in DCs from IBD patients. Human monocyte-derived DCs from IBD patients and healthy controls were exposed to four probiotic strains. The expression of co-stimulatory molecules was assessed and supernatants were analyzed for anti-inflammatory cytokines. The gene expression of toll-like receptors (TLRs), IL-12p40 and integrin αvβ8 were also analyzed. CD80 and CD86 were induced by most probiotic strains in ulcerative colitis (UC) patients whereas only B. bifidum induced CD80 and CD86 expression in Crohn’s disease (CD) patients. IL-10 and TGF-β production was increased in a dose-independent manner while TLR expression was decreased by all probiotic bacteria except B. bifidum in DCs from UC patients. TLR-4 and TLR-9 expression was significantly downregulated while integrin ß8 was significantly increased in the DCs from CD patients. IL-12p40 expression was only significantly downregulated in DCs from CD patients. Our findings point to the general beneficial effects of probiotics in DC immunomodulation and indicate that probiotic bacteria favorably modulate the expression of co-stimulatory molecules, proinflammatory cytokines and TLRs in DCs from IBD patients.

Highlights

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing disorders thought to be multifactorial in origin and involve host immunity, genetic, microbial and environmental factors [1,2]
At day 6 of culture, the immature DCs (iDCs) were analyzed for CD11b, CD11c, CD80 and CD86 markers
The upregulation of Dendritic cells (DCs) surface markers (CD80 and CD86) upon stimulation with probiotic bacteria are presented in Figure 2A–C and Figure 3

Summary

Introduction

Inflammatory bowel diseases (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic, relapsing disorders thought to be multifactorial in origin and involve host immunity, genetic, microbial and environmental factors [1,2]. Several clinical trials are ongoing to explore the effectiveness of tolerogenic DCs (tol-DCs) as an alternative therapeutic option in immune-mediated diseases such CD [6] These clinical-grade tol-DCs have a semimature phenotype that exhibits low levels of T-cell costimulatory properties, and have a reduced capacity to produce proinflammatory cytokines compared to anti-inflammatory molecules, through the expansion and/or induction of regulatory T cells (Treg) [7]. The regular intake of other probiotic species, such as Bacillus subtilis and Bacillus coagulans, contributes to immune modulation by restoring the microbial balance [11,12] These probiotics are currently being used to prevent or treat various clinical conditions, most commonly gastrointestinal disorders [13]. The overall remission rates in patients and/or significant clinical benefits in IBD patients have not been systematically proven, probiotics do provide a benefit in terms of the reduction in disease activity in mild to moderate UC [14]

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Conclusion