Intest Res.  2018 Jul;16(3):384-392. 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

Affiliations
  • 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. nagamakoto@z7.keio.jp takagast@keio.jp
  • 2Department of Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan.
  • 3The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan.

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.

Keyword

Crohn disease; Candida albicans; Tumor necrosis factor-alpha; Dectin-1

MeSH Terms

Blotting, Western
Candida albicans*
Candida*
Crohn Disease*
Cytokines*
Flow Cytometry
Fungi
Healthy Volunteers
Humans
In Vitro Techniques
Inflammation
Interleukin-6
Macrophage Colony-Stimulating Factor
Macrophages*
Microbiota
Monocytes
Mucous Membrane*
Necrosis
Tumor Necrosis Factor-alpha
Cytokines
Interleukin-6
Macrophage Colony-Stimulating Factor
Tumor Necrosis Factor-alpha
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