Characterization of commensal bacteria based on their effects on human dendritic cell-induced T-lymphocyte polarization
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1
Medical and Health Science Center, University of Debrecen, Department of Immunology, Hungary
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2
Uzhorod National University, Department of Microbiology, Immunology, Virology and Aetiology of Infectious Diseases, Ukraine
Enormous diversity of commensal bacteria determines individual functions acting on the development and activities of the human immune system. These involve specialized macrophage and dendritic cell subsets, expression of unique pattern recognition receptor combinations coupled to evolutionally conserved signaling pathways, transcriptional regulation, post-translational modifications, induction of co-stimulatory molecules, secretion of cytokines, chemokines and type I interferons. This complexity can directly be translated to T-lymphocyte polarization to support tolerance induction or inflammation. We have developed a sensitive in vitro culture system for investigating the response of moDC subsets to commensal bacteria by monitoring the expression of type I/II CD1 proteins, phagocytic activity, secretion of chemokines, pro-inflammatory and T-cell polarizing cytokines. Under physiological conditions the gut microenvironment is conditioned by retinoic acid (ATRA) produced by intestinal epithelial cells and CD103+ DCs. To consider the impact of this special microenvironment on moDC-induced T-lymphocyte responses we compared the effects of selected microbes in absence and presence of ATRA. Selected microbes exerted their modulatory effects in a dose- and strain-dependent manner and ATRA had a significant impact on moDC-induced T-cell responses:
• ATRA inhibited CD1a expression in moDCs without affecting CD83 expression;
• Gene expression involved in retinoid synthesis was enhanced but microbes counter acted this effect;
• Secretion of IL-1β concommitant with NOD2, NLRC4 and NLRP12 gene expression was dramatically enhanced by ATRA but microbes inhibited this effect;
• Opposing activity of NOD2 to NLRC4 and NLRP12 pointed to an autocrine IL-1β-mediated regulation;
• ATRA increased Th17 and decreased Th1 responses significantly.
Acknowledgements
This project is supported by TAMOP 4.2.2.A-11/1/KONV-2012-0023, TORNADO FP7-KBBE-2007-2A and OMFB-00331/2009-UA-5/2008.
Keywords:
dendritic cell,
microbiota,
T-Lymphocyte Subsets,
retinoic-acid,
Inflammasomes
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Bene
KP,
Toth
M,
Boyko
N and
Rajnavolgyi
E
(2013). Characterization of commensal bacteria based on their effects on human dendritic cell-induced T-lymphocyte polarization.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00242
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Received:
13 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Mr. Krisztian P Bene, Medical and Health Science Center, University of Debrecen, Department of Immunology, Debrecen, 4012, Hungary, krisztian986@gmail.com