Heat-Killed Fusobacterium nucleatum Triggers Varying Heme-Related Inflammatory and Stress Responses Depending on Primary Human Respiratory Epithelial Cell Type.

Ryo Koike,Hajime Tanaka,Keiko Nodomi,Marni E Cueno,Muneaki Tamura,Kenichi Imai,Ai Kotani,Noriaki Kamio

doi:10.3390/molecules25173839

Ryo Koike, Hajime Tanaka + Show 6 more

Open Access

https://doi.org/10.3390/molecules25173839

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Journal: Molecules (Basel, Switzerland)	Publication Date: Aug 24, 2020
Citations: 10	License type: CC BY 4.0

Affiliation: Nihon University, Tokai University

Abstract

Fusobacterium nucleatum (Fn) is generally an opportunistic oral pathogen that adheres to mammalian mucosal sites, triggering a host inflammatory response. In general, Fn is normally found within the human oral cavity; however, it was previously reported that Fn is a risk factor for certain respiratory diseases. Surprisingly, this was never fully elucidated. Here, we investigated the virulence potential of heat-killed Fn on primary human tracheal, bronchial, and alveolar epithelial cells. In this study, we measured the secretion of inflammatory- (IL-8 and IL-6), stress- (total heme and hydrogen peroxide), and cell death-related (caspase-1 and caspase-3) signals. We established that the inflammatory response mechanism varies in each epithelial cell type: (1) along tracheal cells, possible Fn adherence would trigger increased heme secretion and regulated inflammatory response; (2) along bronchial cells, potential Fn adherence would simultaneously initiate an increase in secreted H2O2 and inflammatory response (ascribable to decreased secreted heme amounts); and (3) along alveolar cells, putative Fn adherence would instigate the increased secretion of inflammatory responses attributable to a decrease in secreted heme levels. Moreover, regardless of the epithelial cell-specific inflammatory mechanism, we believe these are putative, not harmful. Taken together, we propose that any potential Fn-driven inflammation along the respiratory tract would be initiated by differing epithelial cell-specific inflammatory mechanisms that are collectively dependent on secreted heme.

Highlights

Fusobacterium species are Gram-negative, anaerobic bacterial species that are commonly found in mammalian mucosal sites and, the presence of these species along both healthy tissues and disease sites insinuate that these species are opportunistic pathogens [1]
Foreign compounds and pathogens have been known to stimulate the secretion of inflammatory cytokines [16,17,18,19] which, in turn, is affected by the time and robustness of epithelial cell activation leading to the release of high levels of proinflammatory cytokines [20]
The tracheal extracellular IL-8 amount was highest at 12h post-incubation, whereas both extracellular bronchial and alveolar IL-6 amounts were highest at 6h post-incubation

Summary

Introduction

Fusobacterium species are Gram-negative, anaerobic bacterial species that are commonly found in mammalian mucosal sites and, the presence of these species along both healthy tissues and disease sites insinuate that these species are opportunistic pathogens [1]. Molecules 2020, 25, 3839 associated with periodontal disease and implicated in several systemic diseases, including preterm birth and colorectal cancer [2,3,4,5,6]. Fn is a potent stimulator of inflammatory cytokines resulting to exacerbated inflammation [7] which, is one of the traits that make Fn a major pathogen [8]. Taken together, this would imply that Fn-driven inflammation plays a role in disease induction. Respiratory diseases have been considered a risk factor for Fn [9,10] which would suggest that Fn-driven inflammation may contribute to respiratory disease development

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