title: Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells.
abstract: BACKGROUND
  Intestinal homoeostasis is dependent on immunological tolerance to the microbiota.
  
  
  OBJECTIVE
  To (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.
  
  
  METHODS
  Cytokine 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.
  
  
  RESULTS
  Volunteers 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.
  
  
  CONCLUSIONS
  B. 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.
authors: Swiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, Zurich, Switzerland.
authors: Patrycja
authors: P
authors: Konieczna
authors: David
authors: D
authors: Groeger
authors: Mario
authors: M
authors: Ziegler
authors: Remo
authors: R
authors: Frei
authors: Ruth
authors: R
authors: Ferstl
authors: Fergus
authors: F
authors: Shanahan
authors: Eamonn M M
authors: EM
authors: Quigley
authors: Barry
authors: B
authors: Kiely
authors: Cezmi A
authors: CA
authors: Akdis
authors: Liam
authors: L
authors: O'Mahony
mesh_terms: D000328:Adult; D001644:Bifidobacterium / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D004311:Double-Blind Method; D051858:Forkhead Transcription Factors / Q000097:blood*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D053858:Metabolic Networks and Pathways / Q000276:immunology; D019936:Probiotics / Q000494:pharmacology*; D051192:Receptors, Pattern Recognition / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology; D014212:Tretinoin / Q000378:metabolism
chemical_list: D016207:Cytokines; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051192:Receptors, Pattern Recognition; D016753:Interleukin-10; D014212:Tretinoin