Key Elements of Gingival Epithelial Homeostasis upon Bacterial Interaction

Abstract

Epithelia are structurally integral elements in the fabric of oral mucosa with significant functional roles. Similarly, the gingival epithelium performs uniquely critical tasks in responding to a variety of external stimuli and dangers through the regulation of specific built-in molecular mechanisms in a context-dependent fashion at cellular levels. Gingival epithelial cells form an anatomic architecture that confers defense, robustness, and adaptation toward external aggressions, most critically to colonizing microorganisms, among other functions. Accordingly, recent studies unraveled previously uncharacterized response mechanisms in gingival epithelial cells that are constructed to rapidly exert biocidal effects against invader pathobiotic bacteria, such as Porphyromonas gingivalis, through small danger molecule signaling. The host-adapted bacteria, however, have developed adroit strategies to 1) exploit the epithelia as privileged growth niches and 2) chronically target cellular bactericidal and homeostatic metabolic pathways for successful bacterial persistence. As the overgrowth of colonizing microorganisms in the gingival mucosa can shift from homeostasis to dysbiosis or a diseased state, it is crucial to understand how the innate modulatory molecules are intricately involved in antibacterial pathways and how they shape susceptibility versus resistance in the epithelium toward pathogens. Thus, in this review, we highlight recent discoveries in gingival epithelial cell research in the context of bacterial colonizers. The current knowledge outlined here demonstrates the ability of epithelial cells to possess highly organized defense machineries, which can jointly regulate host-derived danger molecule signaling and integrate specific global responses against opportunistic bacteria to combat microbial incursion and maintain host homeostatic balance. These novel examples collectively suggest that the oral epithelia are equipped with a dynamically robust and interconnected defense system encompassing sensors and various effector molecules that arrange and achieve a fine-tuned and advanced response to diverse bacteria.

A bacterial tyrosine phosphatase modulates cell proliferation through targeting RGCC

“…Indeed, P . gingivalis can suppress apoptotic cell death, accelerate cell cycle progression, enhance cell migration, and induce a partial EMT in gingival epithelial cells [ 2 , 4 , 40 – 42 ]. A wealth of information is available regarding specific host effector molecules subverted by P .…”

“…https://doi.org/10.1371/journal.ppat.1009598.t001PLOS PATHOGENSto its biofilm lifestyle, in the oral cavity P. gingivalis engages gingival epithelial cells in an intricate molecular dialogue which can disrupt tissue and immune homeostasis. Indeed, P. gingivalis can suppress apoptotic cell death, accelerate cell cycle progression, enhance cell migration, and induce a partial EMT in gingival epithelial cells[2,4,[40][41][42]. A wealth of information isFig 6.…”

Evaluation of the Effects of E-Cigarette Aerosol Extracts and Tobacco Cigarette Smoke Extracts on Human Gingival Epithelial Cells

“… 19 Dysfunction of GECs in the oral cavity leads to the accumulation of pathogenic bacteria in periodontal tissue, which may lead to the development of periodontitis. 20 …”

“…High levels of ROS cannot be balanced by the antioxidant system, thus causing cell or tissue damage . Dysfunction of GECs in the oral cavity leads to the accumulation of pathogenic bacteria in periodontal tissue, which may lead to the development of periodontitis …”

The Regulatory Effect of Coaggregation Between Fusobacterium nucleatum and Streptococcus gordonii on the Synergistic Virulence to Human Gingival Epithelial Cells

“…The first defense barrier of periodontal tissue against microorganisms is gingival epithelial cells (GECs), which not only form an attachment to the tooth surface, but also form a physical and chemical barrier against infection (Kantrong et al, 2019). GECs can bind to bacteria through special receptors on the cell surface to release antimicrobial peptides such as human b-defensins (hBDs), cytokines, or proteases to resist the invasion of external risk factors and maintain epithelial microecological balance (Handfield et al, 2008;Lee and Yilmaz, 2021). As an opportunistic pathogen, F. nucleatum can not only adhere to and invade GECs (Han et al, 2000;Gursoy et al, 2008;Stathopoulou et al, 2010;Jung et al, 2017;Hung et al, 2018), but also promote the invasion of the nonperiodontal pathogen Streptococcus cristatus into GECs (Edwards et al, 2006).…”