Extracellular Trap Release and Inflammation Induction in Mast Cells by Fusobacterium nucleatum

Authors

    Hiroyuki Tada, Takashi Nishioka, Kenji Matsushita, Sakura Onoue, Kazuyoshi Kawahara Division of Oral Immunology, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi 980-0872, Japan Division of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Sendai, Miyagi 980-0872, Japan Department of Oral Disease Research, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan Department of Biosciences, College of Science and Engineering, Kanto Gakuin University, Kanazawa, Yokohama 236-0037, Japan Department of Biosciences, College of Science and Engineering, Kanto Gakuin University, Kanazawa, Yokohama 236-0037, Japan

Keywords:

Chronic periodontitis, Mast cells, Mast cell-extracellular traps, Fusobacterium nucleatum, Lipopolysaccharide

Abstract

Mast cells play an important role in the innate immune responses to bacterial infections as the first line of defense such as in the skin and mucosa. Mast cells can produce extracellular traps to kill bacteria by trapping pathogens. Mast cell-extracellular traps (MCETs) are composed of web-like DNA fibers that contain bactericidal substances such as DNA, histones, tryptase, and antimicrobial peptides. At present, it is unknown whether the induction of inflammation in periodontal diseases is due to MCETs induced by periodontal bacteria. We investigated the role of mast cells in the induction of MCET production following infection with Fusobacterium nucleatum, a gramnegative anaerobic bacterium associated with periodontal disease. We found that mast cells produced MCETs in response to F. nucleatum infection. Furthermore, the MCETs highly expressed macrophage migration inhibitory factor (MIF). Of note, the level of MIF expressed in the MCETs was inhibited by taurolidine, an LPS antagonist. We next investigated whether MCETs can induce inflammatory responses in monocytes. The MCETs induced the production of IL-1β, IL-6, and IL-8 by monocytes. The production of IL-1β, IL-6, and IL-8 was inhibited by an MIF inhibitor. These findings suggest that MCETs produced by mast cells in response to F. nucleatum infection induce proinflammatory cytokine production by monocytes, which may lead to the chronic inflammation observed in periodontal diseases.

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Published

2020-12-31