Chronic Rhinosinusitis, S. aureus Biofilm and Secreted Products, Inflammatory Responses, and Disease Severity

Abstract

Chronic rhinosinusitis (CRS) is a persistent inflammation of the nasal cavity and paranasal sinuses associated with tissue remodelling, dysfunction of the sinuses' natural defence mechanisms, and induction of different inflammatory clusters. The etiopathogenesis of CRS remains elusive, and both environmental factors, such as bacterial biofilms and the host's general condition, are thought to play a role. Bacterial biofilms have significant clinical relevance due to their potential to cause resistance to antimicrobial therapy and host defenses. Despite substantial medical advances, some CRS patients suffer from recalcitrant disease that is unresponsive to medical and surgical treatments. Those patients often have nasal polyps with tissue eosinophilia, S. aureus-dominant mucosal biofilm, comorbid asthma, and a severely compromised quality of life. This review aims to summarise the contemporary knowledge of inflammatory cells/pathways in CRS, the role of bacterial biofilm, and their impact on the severity of the disease. Here, an emphasis is placed on S. aureus biofilm and its secreted products. A better understanding of these factors might offer important diagnostic and therapeutic perceptions for recalcitrant disease.

Keywords: S. aureus biofilm/virulence factor; chronic rhinosinusitis; inflammatory cells/endotypes.

Figure 1

Virulence factors of Staphylococcus aureus.

Figure 2

Mechanism of type 2 inflammation in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). The dysregulated epithelial barrier results in an enhanced exposure to inhaled pathogens and allergens. In response to environmental stimuli, epithelial cells secrete inflammatory mediators, such as TSLP, IL-25, and IL-33, thus promoting the development of the type 2 immune response. In this pathway, naïve T cells (Th0) differentiate into Th2 cells, leading to the secretion of IL-4, IL-5, and IL-13. Innate immune cells, including ILC2, eosinophils, and mast cells, are activated and release type 2 cytokines that further perpetuate the ongoing inflammatory response and specific granule proteins that contribute to tissue injury. B cells and activated plasma cells are also increased, thus contributing to the enhanced local generation of antibodies. Type 2 cytokines can result in decreased tissue plasminogen activator and increased FXIIIA levels, which, in a state of an increased vascular leak, can lead to enhanced fibrin cross-linking and deposition within nasal polyps. In a type 2 inflammatory pathway with a general lack of regulatory T cells function, IL-5 triggers eosinophilia, and IL-4 and IL-13 are responsible for local IgE production by B cells. Furthermore, IL-4 and IL-13 lead to goblet cells hyperplasia and excess mucus production.

Figure 3

Mechanisms of non-type 2 inflammation in patients with chronic rhinosinusitis without nasal polyps (CRSsNP). In response to environmental stimuli, epithelial cells release inflammatory mediators that induce type 1 (Th1) or 17 (Th17) inflammatory pathways. Th1 and Th17 orchestrate inflammation through the production of IFN-γ, IL-17a, and IL-22. In this pathway, B cell activation and differentiation into plasma cells can produce IgG antibodies that finally lead to neutrophil activation.