Wheat-derived arabinoxylans reduced M2-macrophage functional activity, but enhanced monocyte-recruitment capacity.

Coen Govers,Harry J Wichers,Ellen H Stolte,Jurriaan J Mes,Yongfu Tang

doi:10.1039/d0fo00316f

Abstract

The immunomodulatory properties of non-digestible polysaccharides (NDPs) have been recognized in in vitro and in vivo studies. The latter mostly demonstrated altered frequencies and inflammatory status of immune cells as clinical parameters. Most of the NDP activity will be exerted in the intestine where they can directly interact with macrophages. The predominant macrophage phenotype in the intestine is M2-like, with M1-like macrophages arising during inflammation. Here, we investigated transcriptional and functional impact on these macrophage phenotypes by NDP-treatment (i.e. yeast-derived soluble β-glucan (yeast-βG), apple-derived RG-I (apple-RGI), shiitake-derived β-glucan (shiitake-βG) or wheat-derived arabinoxylan (wheat-AX)). Wheat-AX, and to a lesser extent shiitake-βG and apple-RGI but not yeast-βG, reduced endocytosis and antigen processing capacity of M1- and M2-like macrophages. Moreover, the NDPs, and most notably wheat-AX, strongly induced transcription and secretion of a unique set of cytokines and chemokines. Conditioned medium from wheat-AX-treated M2-like macrophages subsequently demonstrated strongly increased monocyte recruitment capacity. These findings are in line with clinically observed immunomodulatory aspects of NDPs making it tempting to speculate that clinical activity of some NDPs is mediated through enhanced chemoattraction and modifying activity of intestinal immune cells.

Highlights

Non-digestible polysaccharides (NDPs) constitute a large family of different molecules, including β-glucans, pectins, resistant starch, cellulose and arabinoxylans, and are known for their immune-modulatory properties and beneficial health effects.[1,2] These properties were demonstrated in vitro as well as reported in clinical studies using different NDPs
Tested signaling molecules were selected based on gene transcription levels of M1-like macrophages, with typically and/or significantly increased transcription of CXCL9, CXCL10, CXCL11, and TNFα, M2-like macrophages, with a strongest and significant increase in CCL24 transcription, and NDP-treated macrophages, with typically and/or significantly increased CCL1, CCL5, CCL20, CXCL8, IL-1β, and MMP-1 transcription for most NDPs (ESI Table 1†)
These findings are in line with reduced gene transcription in NDP-treated macrophages of NDPbinding lectin-receptors (i.e. CD302, MERTK and dectin124,27,28) and HLA-class II molecules for lysosomal antigen loading (i.e. HLA-DM and HLA-DO (ESI Table 2†)29)

Summary

Introduction

Non-digestible polysaccharides (NDPs) constitute a large family of different molecules, including β-glucans, pectins, resistant starch, cellulose and arabinoxylans, and are known for their immune-modulatory properties and beneficial health effects.[1,2] These properties were demonstrated in vitro as well as reported in clinical studies using different NDPs. Other beneficial health effects related to NDP intake reported in clinical trials include increased NK cell activity linked to a reduction in metastasis in lung and breast cancer patients;[6] increased blood leukocytes, neutrophils, IgG and IgM frequencies accompanied by delayed progression of non-small cell lung cancer;[7] and transiently increased blood levels of IgG and IgM and NK cell counts linked to a reduction in flu and flu-like symptoms and respiratory tract infections in children.[8]

Methods

Results

Conclusion