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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Colitogenic and non-colitogenic commensal bacteria differentially trigger DC maturation and Th cell polarization: an
Julia S Frick1, Naima Zahir, Martina Müller
1Institute of Medical Microbiology and Hygiene, University of Tübingen, Germany. julia-stefanie.frick@med.uni-tuebingen.de
Abstract:
We investigated whether commensal bacteria modulate activation and maturation of bone marrow-derived DC and their ability to prime CD4(+) T cells. We used Escherichia coli mpk, which induces colitis in gnotobiotic IL-2-deficient (IL-2(-/-)) mice, and Bacteroides vulgatus mpk, which prevents E. coli-induced colitis. Stimulation of DC with E. coli induced TNF-alpha, IL-12 and IL-6 secretion and expression of activation markers. Moreover, stimulation of DC with E. coli increased T cell activation and led to Th1 polarization. Stimulation with B. vulgatus led only to secretion of IL-6, and DC were driven into a semi-mature state with low expression of activation markers and did not promote Th1 responses. B. vulgatus-induced semi-mature DC were non-responsive to stimulation by E. coli in terms of maturation, T cell priming and TNF-alpha but not IL-6 production. The non-responsiveness of B. vulgatus-stimulated DC was abrogated by addition of anti-IL-6 mAb or mimicked with rIL-6. These data suggest that B. vulgatus-induced IL-6 drives DC into a semi-mature state in which they are non-responsive to proinflammatory activation by E. coli. This in vitro mechanism might contribute to the prevention of E. coli-triggered colitis development by B. vulgatus in vivo; high IL-6 mRNA expression was consistently found in B. vulgatus-colonized or B. vulgatus/E. coli co-colonized IL-2(-/-) mice and was associated with absence of colitis.
Insights
Commensal bacteria, Bacteroides vulgatus, prevent colitis by inducing semi-mature dendritic cells (DCs) via IL-6. These semi-mature DCs are unresponsive to pro-inflammatory E. coli, protecting against colitis.
Area of Science:
- Immunology
- Microbiology
- Gastroenterology
Background:
- Commensal bacteria play a crucial role in host immune homeostasis.
- Dendritic cells (DCs) are key antigen-presenting cells that bridge innate and adaptive immunity.
- Dysbiosis and inflammation contribute to inflammatory bowel diseases like colitis.
Purpose of the Study:
- To investigate how commensal bacteria modulate dendritic cell (DC) activation and maturation.
- To determine the impact of DC modulation on CD4(+) T cell priming.
- To elucidate the mechanism by which Bacteroides vulgatus prevents E. coli-induced colitis.
Main Methods:
- Utilized gnotobiotic IL-2-deficient mice challenged with Escherichia coli and Bacteroides vulgatus.
- Stimulated bone marrow-derived DCs with E. coli and B. vulgatus.
- Assessed DC activation markers, cytokine secretion (TNF-alpha, IL-12, IL-6), and T cell priming (Th1 polarization).
- Investigated the role of IL-6 in DC hyporesponsiveness using anti-IL-6 mAb and recombinant IL-6 (rIL-6).
Main Results:
- E. coli stimulation induced DC maturation, pro-inflammatory cytokine secretion (TNF-alpha, IL-12, IL-6), and Th1 polarization.
- B. vulgatus stimulation led to IL-6 secretion, driving DCs into a semi-mature state with low activation markers.
- Semi-mature DCs induced by B. vulgatus were hyporesponsive to E. coli activation, except for IL-6 production.
- IL-6 was identified as the key mediator of B. vulgatus-induced DC hyporesponsiveness.
- High IL-6 mRNA expression correlated with the absence of colitis in B. vulgatus-colonized mice.
Conclusions:
- Bacteroides vulgatus induces a semi-mature dendritic cell phenotype through IL-6 secretion.
- This IL-6-mediated semi-maturation renders DCs hyporesponsive to pro-inflammatory stimuli like E. coli.
- This mechanism likely contributes to the protective effect of B. vulgatus against E. coli-induced colitis in vivo.
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