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Erschienen in: European Journal of Nutrition 1/2016

01.02.2016 | Original Contribution

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

verfasst von: Jean-François Mallet, Émilie Graham, Barry W. Ritz, Kohei Homma, Chantal Matar

Erschienen in: European Journal of Nutrition | Ausgabe 1/2016

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Abstract

Purpose

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.
Literatur
1.
Zurück zum Zitat Ritz BW, Nogusa S, Ackerman EA, Gardner EM (2006) Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. J Nutr 136(11):2868–2873 Ritz BW, Nogusa S, Ackerman EA, Gardner EM (2006) Supplementation with active hexose correlated compound increases the innate immune response of young mice to primary influenza infection. J Nutr 136(11):2868–2873
2.
Zurück zum Zitat Ritz BW (2008) Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. Nutr Rev 66(9):526–531CrossRef Ritz BW (2008) Supplementation with active hexose correlated compound increases survival following infectious challenge in mice. Nutr Rev 66(9):526–531CrossRef
3.
Zurück zum Zitat Nogusa S, Gerbino J, Ritz BW (2009) Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 29(2):139–143CrossRef Nogusa S, Gerbino J, Ritz BW (2009) Low-dose supplementation with active hexose correlated compound improves the immune response to acute influenza infection in C57BL/6 mice. Nutr Res. 29(2):139–143CrossRef
4.
Zurück zum Zitat Daddaoua A, Martínez-Plata E, Ortega-González M, Ocón B, Aranda CJ, Zarzuelo A et al (2013) The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation. Food Chem 136(3–4):1288–1295CrossRef Daddaoua A, Martínez-Plata E, Ortega-González M, Ocón B, Aranda CJ, Zarzuelo A et al (2013) The nutritional supplement Active Hexose Correlated Compound (AHCC) has direct immunomodulatory actions on intestinal epithelial cells and macrophages involving TLR/MyD88 and NF-κB/MAPK activation. Food Chem 136(3–4):1288–1295CrossRef
5.
Zurück zum Zitat Miura T, Kitadate K, Nishioka H, Wakame K (2010) Basic and clinical studies on active hexose correlated compound. In: Bagchi D, Lau FC, Ghosh DK (eds) Biotechnology in functional foods and nutraceuticals. CRC Press, Boca Raton, pp 51–60CrossRef Miura T, Kitadate K, Nishioka H, Wakame K (2010) Basic and clinical studies on active hexose correlated compound. In: Bagchi D, Lau FC, Ghosh DK (eds) Biotechnology in functional foods and nutraceuticals. CRC Press, Boca Raton, pp 51–60CrossRef
6.
Zurück zum Zitat Okuyama T, Yoshigai E, Ikeya Y, Nishizawa M (2013) Active Hexose Correlated Compound extends the lifespan and increases the thermotolerance of nematodes. Funct Foods Health Dis 3(6):166–182 Okuyama T, Yoshigai E, Ikeya Y, Nishizawa M (2013) Active Hexose Correlated Compound extends the lifespan and increases the thermotolerance of nematodes. Funct Foods Health Dis 3(6):166–182
7.
Zurück zum Zitat Shah VB, Williams DL, Keshvara L (2009) β-Glucan attenuates TLR2- and TLR4-mediated cytokine production by microglia. Neurosci Lett 458(3):111–115CrossRef Shah VB, Williams DL, Keshvara L (2009) β-Glucan attenuates TLR2- and TLR4-mediated cytokine production by microglia. Neurosci Lett 458(3):111–115CrossRef
8.
Zurück zum Zitat Shah VB, Huang Y, Keshwara R, Ozment-Skelton T, Williams DL, Keshvara L (2008) Beta-glucan activates microglia without inducing cytokine production in Dectin-1-dependent manner. J Immunol 180(5):2777–2785CrossRef Shah VB, Huang Y, Keshwara R, Ozment-Skelton T, Williams DL, Keshvara L (2008) Beta-glucan activates microglia without inducing cytokine production in Dectin-1-dependent manner. J Immunol 180(5):2777–2785CrossRef
9.
Zurück zum Zitat Zhu W, Ma H, Miao J, Huang G, Tong M, Zou S (2013) β-Glucan modulates the lipopolysaccharide-induced innate immune response in rat mammary epithelial cells. Int Immunopharmacol 15(2):457–465CrossRef Zhu W, Ma H, Miao J, Huang G, Tong M, Zou S (2013) β-Glucan modulates the lipopolysaccharide-induced innate immune response in rat mammary epithelial cells. Int Immunopharmacol 15(2):457–465CrossRef
10.
Zurück zum Zitat Spierings ELH, Fujii H, Sun B, Walshe T (2007) A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. J Nutr Sci Vitaminol (Tokyo) 53(6):536–539CrossRef Spierings ELH, Fujii H, Sun B, Walshe T (2007) A Phase I study of the safety of the nutritional supplement, active hexose correlated compound, AHCC, in healthy volunteers. J Nutr Sci Vitaminol (Tokyo) 53(6):536–539CrossRef
11.
Zurück zum Zitat Shah SK, Walker PA, Moore-Olufemi SD, Sundaresan A, Kulkarni AD, Andrassy RJ (2011) An evidence-based review of a Lentinula edodes mushroom extract as complementary therapy in the surgical oncology patient. J Parenter Enter Nutr 35(4):449–458CrossRef Shah SK, Walker PA, Moore-Olufemi SD, Sundaresan A, Kulkarni AD, Andrassy RJ (2011) An evidence-based review of a Lentinula edodes mushroom extract as complementary therapy in the surgical oncology patient. J Parenter Enter Nutr 35(4):449–458CrossRef
12.
Zurück zum Zitat Kay E, Scotland RS, Whiteford JR (2014) Toll-like receptors: role in inflammation and therapeutic potential. BioFactors 40(3):284–294CrossRef Kay E, Scotland RS, Whiteford JR (2014) Toll-like receptors: role in inflammation and therapeutic potential. BioFactors 40(3):284–294CrossRef
13.
Zurück zum Zitat Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124(4):783–801CrossRef Akira S, Uematsu S, Takeuchi O (2006) Pathogen recognition and innate immunity. Cell 124(4):783–801CrossRef
14.
Zurück zum Zitat Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS (2000) Toll-like receptor 4, but not Toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol 165(10):5780–5787CrossRef Tapping RI, Akashi S, Miyake K, Godowski PJ, Tobias PS (2000) Toll-like receptor 4, but not Toll-like receptor 2, is a signaling receptor for Escherichia and Salmonella lipopolysaccharides. J Immunol 165(10):5780–5787CrossRef
15.
Zurück zum Zitat Gould D. (2010) Causes, prevention and treatment of Escherichia coli infections. Nurs Stand 7;24(31):50–56; quiz 58 Gould D. (2010) Causes, prevention and treatment of Escherichia coli infections. Nurs Stand 7;24(31):50–56; quiz 58
16.
Zurück zum Zitat Dho-Moulin M, Fairbrother JM (1999) Avian pathogenic Escherichia coli (APEC). Vet Res 30(2–3):299–316 Dho-Moulin M, Fairbrother JM (1999) Avian pathogenic Escherichia coli (APEC). Vet Res 30(2–3):299–316
17.
Zurück zum Zitat Kaper JB, Nataro JP, Mobley HLT (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2(2):123–140CrossRef Kaper JB, Nataro JP, Mobley HLT (2004) Pathogenic Escherichia coli. Nat Rev Microbiol 2(2):123–140CrossRef
18.
Zurück zum Zitat Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PSC, Goulet J, Tompkins TA (2005) Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-Induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect Immun 73(8):5183–5188CrossRef Sherman PM, Johnson-Henry KC, Yeung HP, Ngo PSC, Goulet J, Tompkins TA (2005) Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-Induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect Immun 73(8):5183–5188CrossRef
19.
Zurück zum Zitat Abreu MT, Thomas LS, Arnold ET, Lukasek K, Michelsen KS, Arditi M (2003) TLR signaling at the intestinal epithelial interface. J Endotoxin Res 9(5):322–330CrossRef Abreu MT, Thomas LS, Arnold ET, Lukasek K, Michelsen KS, Arditi M (2003) TLR signaling at the intestinal epithelial interface. J Endotoxin Res 9(5):322–330CrossRef
20.
Zurück zum Zitat Vinderola G, Matar C, Perdigón G (2005) Role of intestinal epithelial cells in immune effects mediated by Gram-positive probiotic bacteria: involvement of Toll-like receptors. Clin Diagn Lab Immunol 12(9):1075–1084 Vinderola G, Matar C, Perdigón G (2005) Role of intestinal epithelial cells in immune effects mediated by Gram-positive probiotic bacteria: involvement of Toll-like receptors. Clin Diagn Lab Immunol 12(9):1075–1084
21.
Zurück zum Zitat Otte J-M, Cario E, Podolsky DK (2004) Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology 126(4):1054–1070CrossRef Otte J-M, Cario E, Podolsky DK (2004) Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology 126(4):1054–1070CrossRef
22.
Zurück zum Zitat Sainte-Marie G (1962) A paraffin embedding technique for studies employing immunofluorescence. J Histochem Cytochem 10(3):250–256CrossRef Sainte-Marie G (1962) A paraffin embedding technique for studies employing immunofluorescence. J Histochem Cytochem 10(3):250–256CrossRef
23.
Zurück zum Zitat Slorach EM, Campbell FC, Dorin JR (1999) A mouse model of intestinal stem cell function and regeneration. J Cell Sci 112(18):3029–3038 Slorach EM, Campbell FC, Dorin JR (1999) A mouse model of intestinal stem cell function and regeneration. J Cell Sci 112(18):3029–3038
24.
Zurück zum Zitat Dogi CA, Galdeano CM, Perdigón G (2008) Gut immune stimulation by non pathogenic Gram(+) and Gram(−) bacteria. Comparison with a probiotic strain. Cytokine. 41(3):223–231CrossRef Dogi CA, Galdeano CM, Perdigón G (2008) Gut immune stimulation by non pathogenic Gram(+) and Gram(−) bacteria. Comparison with a probiotic strain. Cytokine. 41(3):223–231CrossRef
25.
Zurück zum Zitat Mantis NJ, Rol N, Corthésy B (2011) Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4(6):603–611CrossRef Mantis NJ, Rol N, Corthésy B (2011) Secretory IgA’s complex roles in immunity and mucosal homeostasis in the gut. Mucosal Immunol 4(6):603–611CrossRef
26.
Zurück zum Zitat Brandtzaeg P (2007) Induction of secretory immunity and memory at mucosal surfaces. Vaccine 25(30):5467–5484CrossRef Brandtzaeg P (2007) Induction of secretory immunity and memory at mucosal surfaces. Vaccine 25(30):5467–5484CrossRef
27.
Zurück zum Zitat Aviles H, O’Donnell P, Orshal J, Fujii H, Sun B, Sonnenfeld G (2008) Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection. Am J Surg 195(4):537–545CrossRef Aviles H, O’Donnell P, Orshal J, Fujii H, Sun B, Sonnenfeld G (2008) Active hexose correlated compound activates immune function to decrease bacterial load in a murine model of intramuscular infection. Am J Surg 195(4):537–545CrossRef
28.
Zurück zum Zitat Wong EB, Mallet J-F, Duarte J, Matar C, Ritz BW (2014) Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4. Nutr Res 34(4):318–325CrossRef Wong EB, Mallet J-F, Duarte J, Matar C, Ritz BW (2014) Bovine colostrum enhances natural killer cell activity and immune response in a mouse model of influenza infection and mediates intestinal immunity through toll-like receptors 2 and 4. Nutr Res 34(4):318–325CrossRef
29.
Zurück zum Zitat Wang Y, Ames N, Li S, Jones P, Khafipour E (2014) High molecular weight barley β-glucan supports bacterial populations beneficial for gut health. FASEB J 28(1 Supplement):647.45 Wang Y, Ames N, Li S, Jones P, Khafipour E (2014) High molecular weight barley β-glucan supports bacterial populations beneficial for gut health. FASEB J 28(1 Supplement):647.45
Metadaten
Titel
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
verfasst von
Jean-François Mallet
Émilie Graham
Barry W. Ritz
Kohei Homma
Chantal Matar
Publikationsdatum
01.02.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
European Journal of Nutrition / Ausgabe 1/2016
Print ISSN: 1436-6207
Elektronische ISSN: 1436-6215
DOI
https://doi.org/10.1007/s00394-015-0832-2

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