Journal Article

Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells

Ziegler, Mario, O'Mahony, Liam, Groeger, David, Shanahan, Fergus, Quigley, Eamonn M M, Frei, Remo, Ferstl, Ruth, Akdis, Cezmi A, Konieczna, Patrycja, Kiely, Barry

2012

Overview

BackgroundIntestinal homoeostasis is dependent on immunological tolerance to the microbiota.ObjectiveTo (1) determine if a probiotic could induce Foxp3 T cells in humans; (2) to elucidate the molecular mechanisms, which are involved in the induction of Foxp3 T cells by human dendritic cells.DesignCytokine secretion and Foxp3 expression were assessed in human volunteers following Bifidobacterium infantis feeding. Monocyte-derived dendritic cells (MDDCs), myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) were incubated in vitro with B infantis and autologous lymphocytes. Transcription factor expression, costimulatory molecule expression, cytokine secretion, retinoic acid and tryptophan metabolism were analysed.ResultsVolunteers fed B infantis displayed a selective increase in secretion of interleukin (IL)-10 and enhanced Foxp3 expression in peripheral blood. In vitro, MDDCs, mDCs and pDCs expressed indoleamine 2,3-dioxygenase and secreted IL-10, but not IL-12p70, in response to B infantis. MDDC and mDC IL-10 secretion was Toll-like receptor (TLR)-2/6 dependent, while pDC IL-10 secretion was TLR-9 dependent. In addition, MDDCs and mDCs expressed RALDH2, which was TLR-2 and DC-SIGN dependent. B infantis-stimulated MDDCs, mDCs and pDCs induced T cell Foxp3 expression. TLR-2, DC-SIGN and retinoic acid were required for MDDC and mDC induction of Foxp3 T cells, while pDCs required indoleamine 2,3-dioxygenase.ConclusionsB infantis administration to humans selectively promotes immunoregulatory responses, suggesting that this microbe may have therapeutic utility in patients with inflammatory disease. Cross-talk between multiple pattern-recognition receptors and metabolic pathways determines the innate and subsequent T regulatory cell response to B infantis. These findings link nutrition, microbiota and the induction of tolerance within the gastrointestinal mucosa.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Adult / anti-bacterial mucosal immunity / Antigens / Bacteria / bifidobacteria / Bifidobacterium - immunology / Bifidobacterium infantis / Biological and medical sciences / Cell Communication - immunology / Cells, Cultured / cellular immunology / Coculture Techniques / coeliac disease / constipation / Costimulator / Cytokines / Cytokines - blood / DC-SIGN protein / Dendritic cells / Dendritic Cells - immunology / Digestive tract / Double-Blind Method / Feeding / Forkhead Transcription Factors - blood / Foxp3 protein / gastric emptying / Gastroenterology. Liver. Pancreas. Abdomen / gastroparesis / Gene expression / histamine / Humans / Immunological tolerance / Immunoregulation / inflammation / Inflammatory bowel disease / Inflammatory diseases / Interleukin 10 / Interleukin 12 / Interleukin-10 - blood / intestinal transplantation / Intestine / irritable bowel syndrome / Lymphocytes / Lymphocytes B / Lymphocytes T / Medical sciences / Metabolic Networks and Pathways - immunology / Metabolic pathways / microbiota / molecular immunology / Molecular modelling / Monocytes / Mucosa / mucosal immunology / mucosal tolerance / Nutrition / Peripheral blood / probiotics / Probiotics - pharmacology / Receptors, Pattern Recognition - immunology / Retinoic acid / Rodents / Studies / T cell receptors / T lymphocytes / T regulatory cells / T-Lymphocytes, Regulatory - drug effects / T-Lymphocytes, Regulatory - immunology / TLR2 protein / TLR9 protein / Toll-like receptors / Transcription factors / Tretinoin - metabolism / Tryptophan / Tryptophan 2,3-dioxygenase / Volunteers