title: Active Hexose Correlated Compound (AHCC) promotes an intestinal immune response in BALB/c mice and in primary intestinal epithelial cell culture involving toll-like receptors TLR-2 and TLR-4.
abstract: OBJECTIVE
  Active Hexose Correlated Compound (AHCC(®)) is a cultured mushroom extract that is commercially available and promoted for immune support. Available data suggest that AHCC supplementation affects immune cell populations and immune outcomes, including natural killer cell response to infection. The mechanism by which AHCC exerts its effects is not well understood. The present work aimed to characterize the immunomodulatory activity of AHCC in the gut and to study the effects of AHCC on toll-like receptor (TLR) signaling in intestinal epithelial cells (IECs).
  
  
  METHODS
  BALB/c mice were fed AHCC by gavage. In vivo activities were assessed by immunohistochemistry and cytokine production. The effects of AHCC on ex vivo primary cell culture from IECs were examined after challenge with LPS or E. coli alone or in the presence of anti-TLR-2 and TLR-4 blocking antibodies.
  
  
  RESULTS
  Feeding AHCC resulted in increased IgA+ cells in the intestine and increased sIgA, IL-10, and IFN-γ in the intestinal fluid. In IECs, contact with AHCC increased IL-6 production but not to the pro-inflammatory level of positive controls, LPS and E. coli. Blocking TLR-2 and TLR-4 reduced the induction of IL-6 by AHCC, suggesting that these innate receptors are involved in generating the immune response of IECs to AHCC.
  
  
  CONCLUSIONS
  AHCC may play a role in the orchestration of immune response and the maintenance of immune homeostasis in part by priming the TLR-2 and TLR-4 gate at the intestinal epithelium. Such a response is likely due to the recognition of non-pathogenic food-associated molecular patterns (FAMPs) such as those found associated with other mushroom or yeast-derived compounds.
authors.affiliation: Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mallet
authors.affiliation: Nutrition Sciences Program, Faculty of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada.
authors.forename: Émilie
authors.initials: É
authors.lastname: Graham
authors.affiliation: Nutrition Sciences Department, College of Nursing and Health Professions, Drexel University, 245 N. 15th Street, Mail Stop 1030, Philadelphia, PA, 19102, USA.
authors.forename: Barry W
authors.initials: BW
authors.lastname: Ritz
authors.affiliation: Amino Up Chemical Company, Ltd., 363-32 Shin-ei, Kiyota-ku, Sapporo, 004-0839, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Homma
authors.affiliation: Nutrition Sciences Program, Faculty of Health Sciences, University of Ottawa, 451 Smyth Road, Ottawa, ON, K1H 8M5, Canada. chantal.matar@uottawa.ca.
authors.forename: Chantal
authors.initials: C
authors.lastname: Matar
mesh_terms: D000363:Agaricales / Q000737:chemistry; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology*; D004926:Escherichia coli; D005260:Female; D007070:Immunoglobulin A / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D011134:Polysaccharides / Q000494:pharmacology*; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: C000611649:IFNG protein, mouse; C556062:IL10 protein, mouse; D007070:Immunoglobulin A; D015850:Interleukin-6; D011134:Polysaccharides; C493486:Tlr2 protein, mouse; C493487:Tlr4 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D007371:Interferon-gamma; C499366:Active Hexose Correlated Compound
keywords: AHCC; E. coli; FAMP; Infection; Innate; Mushroom; Toll-like receptor