Intest Res 2018; 16(3): 384-392  https://doi.org/10.5217/ir.2018.16.3.384
β-(1,3)-Glucan derived from Candida albicans induces inflammatory cytokines from macrophages and lamina propria mononuclear cells derived from patients with Crohn’s disease
Kiyoto Mori1, Makoto Naganuma1, Shinta Mizuno1, Hiroaki Suzuki1, Mina T. Kitazume1, Katsuyoshi Shimamura1, Sayako Chiba1, Akira Sugita2, Katsuyoshi Matsuoka1, Tadakazu Hisamatsu3, Takanori Kanai1
1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, 2Department of Surgery, Yokohama Municipal Citizen’s Hospital, Yokohama, 3The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan
Correspondence to: Makoto Naganuma, Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Tel: +81-3-3353-1211, Fax: +81-3-5363-3670, E-mail: nagamakoto@z7.keio.jp
Co-Correspondence to Takanori Kanai, Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. Tel: +81-3-3353-1211, Fax: +81-3-3341-3631, E-mail: takagast@keio.jp
Received: November 20, 2017; Revised: December 20, 2017; Accepted: December 22, 2017; Published online: February 20, 2018.
© Korean Association for the Study of Intestinal Diseases. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn’s disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. Methods: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mφs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mφs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. Results: Mγ-Mφs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mφs than in M-Mφs. The increase in TNF-α production by Mγ-Mφs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. Conclusions: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.
Keywords: Crohn disease; Candida albicans; Tumor necrosis factor-alpha; Dectin-1


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