Publication

Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis

Sahasrabudhe, N. M., Beukema, M., Tian, L., Troost, B., Scholte, J., Bruininx, E., Bruggeman, G., van den Berg, M., Scheurink, A., Schols, H. A., Faas, M. M. & de Vos, P., 1-Mar-2018, In : Frontiers in Immunology. 9, 19 p., 383.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Sahasrabudhe, N. M., Beukema, M., Tian, L., Troost, B., Scholte, J., Bruininx, E., ... de Vos, P. (2018). Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis. Frontiers in Immunology, 9, [383]. https://doi.org/10.3389/fimmu.2018.00383

Author

Sahasrabudhe, Neha M. ; Beukema, Martin ; Tian, Lingmin ; Troost, Berit ; Scholte, Jan ; Bruininx, Erik ; Bruggeman, Geert ; van den Berg, Marco ; Scheurink, Anton ; Schols, Henk A. ; Faas, Marijke M. ; de Vos, Paul. / Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis. In: Frontiers in Immunology. 2018 ; Vol. 9.

Harvard

Sahasrabudhe, NM, Beukema, M, Tian, L, Troost, B, Scholte, J, Bruininx, E, Bruggeman, G, van den Berg, M, Scheurink, A, Schols, HA, Faas, MM & de Vos, P 2018, 'Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis', Frontiers in Immunology, vol. 9, 383. https://doi.org/10.3389/fimmu.2018.00383

Standard

Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis. / Sahasrabudhe, Neha M.; Beukema, Martin; Tian, Lingmin; Troost, Berit; Scholte, Jan; Bruininx, Erik; Bruggeman, Geert; van den Berg, Marco; Scheurink, Anton; Schols, Henk A.; Faas, Marijke M.; de Vos, Paul.

In: Frontiers in Immunology, Vol. 9, 383, 01.03.2018.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Sahasrabudhe NM, Beukema M, Tian L, Troost B, Scholte J, Bruininx E et al. Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis. Frontiers in Immunology. 2018 Mar 1;9. 383. https://doi.org/10.3389/fimmu.2018.00383


BibTeX

@article{e30a46bcf1db4f73ae3a2b444ac4f665,
title = "Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis",
abstract = "Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered. This effect is most pronounced with pectins having a low degree of methyl esterification (DM). Low-DM pectin interacts with TLR2 through electrostatic forces between non-esterified galacturonic acids on the pectin and positive charges on the TLR2 ectodomain, as confirmed by testing pectin binding on mutated TLR2. The anti-inflammatory effect of low-DM pectins was first studied in human dendritic cells and mouse macrophages in vitro and was subsequently tested in vivo in TLR2-dependent ileitis in a mouse model. In these mice, ileitis was prevented by pectin administration. Protective effects were shown to be TLR2-TLR1 dependent and independent of the SCFAs produced by the gut microbiota. These data suggest that low-DM pectins as a source of dietary fiber can reduce inflammation through direct interaction with TLR2-TLR1 receptors.",
keywords = "dietary fiber, toll-like receptor 2, pectin, ileitis, degree of methyl esterification, DENDRITIC CELLS, DIACYLATED LIPOPEPTIDES, DECTIN-1 ACTIVATION, BARRIER FUNCTION, CITRUS PECTIN, MOUSE MODEL, RECOGNITION, INFLAMMATION, METABOLITES, MICROBIOTA",
author = "Sahasrabudhe, {Neha M.} and Martin Beukema and Lingmin Tian and Berit Troost and Jan Scholte and Erik Bruininx and Geert Bruggeman and {van den Berg}, Marco and Anton Scheurink and Schols, {Henk A.} and Faas, {Marijke M.} and {de Vos}, Paul",
year = "2018",
month = "3",
day = "1",
doi = "10.3389/fimmu.2018.00383",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media SA",

}

RIS

TY - JOUR

T1 - Dietary fiber pectin directly blocks toll-like receptor 2-1 and prevents doxorubicin-induced ileitis

AU - Sahasrabudhe, Neha M.

AU - Beukema, Martin

AU - Tian, Lingmin

AU - Troost, Berit

AU - Scholte, Jan

AU - Bruininx, Erik

AU - Bruggeman, Geert

AU - van den Berg, Marco

AU - Scheurink, Anton

AU - Schols, Henk A.

AU - Faas, Marijke M.

AU - de Vos, Paul

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered. This effect is most pronounced with pectins having a low degree of methyl esterification (DM). Low-DM pectin interacts with TLR2 through electrostatic forces between non-esterified galacturonic acids on the pectin and positive charges on the TLR2 ectodomain, as confirmed by testing pectin binding on mutated TLR2. The anti-inflammatory effect of low-DM pectins was first studied in human dendritic cells and mouse macrophages in vitro and was subsequently tested in vivo in TLR2-dependent ileitis in a mouse model. In these mice, ileitis was prevented by pectin administration. Protective effects were shown to be TLR2-TLR1 dependent and independent of the SCFAs produced by the gut microbiota. These data suggest that low-DM pectins as a source of dietary fiber can reduce inflammation through direct interaction with TLR2-TLR1 receptors.

AB - Dietary carbohydrate fibers are known to prevent immunological diseases common in Western countries such as allergy and asthma but the underlying mechanisms are largely unknown. Until now beneficial effects of dietary fibers are mainly attributed to fermentation products of the fibers such as anti-inflammatory short-chain fatty acids (SCFAs). Here, we found and present a new mechanism by which dietary fibers can be anti-inflammatory: a commonly consumed fiber, pectin, blocks innate immune receptors. We show that pectin binds and inhibits, toll-like receptor 2 (TLR2) and specifically inhibits the proinflammatory TLR2-TLR1 pathway while the tolerogenic TLR2-TLR6 pathway remains unaltered. This effect is most pronounced with pectins having a low degree of methyl esterification (DM). Low-DM pectin interacts with TLR2 through electrostatic forces between non-esterified galacturonic acids on the pectin and positive charges on the TLR2 ectodomain, as confirmed by testing pectin binding on mutated TLR2. The anti-inflammatory effect of low-DM pectins was first studied in human dendritic cells and mouse macrophages in vitro and was subsequently tested in vivo in TLR2-dependent ileitis in a mouse model. In these mice, ileitis was prevented by pectin administration. Protective effects were shown to be TLR2-TLR1 dependent and independent of the SCFAs produced by the gut microbiota. These data suggest that low-DM pectins as a source of dietary fiber can reduce inflammation through direct interaction with TLR2-TLR1 receptors.

KW - dietary fiber

KW - toll-like receptor 2

KW - pectin

KW - ileitis

KW - degree of methyl esterification

KW - DENDRITIC CELLS

KW - DIACYLATED LIPOPEPTIDES

KW - DECTIN-1 ACTIVATION

KW - BARRIER FUNCTION

KW - CITRUS PECTIN

KW - MOUSE MODEL

KW - RECOGNITION

KW - INFLAMMATION

KW - METABOLITES

KW - MICROBIOTA

U2 - 10.3389/fimmu.2018.00383

DO - 10.3389/fimmu.2018.00383

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 383

ER -

ID: 55624317