Immune Mechanisms of Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a common inflammatory disease that results in a significant decrease in patient quality of life and a large economic burden. However, the lack of population-based epidemiologic studies and robust model systems has made it difficult to fully elucidate the key inflammatory pathways that drive the chronic inflammatory responses observed in CRS. This review will highlight the wide variety of factors that likely contribute to CRS disease pathogenesis. Defects in the innate immune function of the airway epithelium, including decreases in barrier function, mucociliary clearance, and production of antimicrobial peptides, all likely play a role in the initial inflammatory response. Subsequent recruitment and activation of eosinophils, mast cells, and innate lymphoid cells (ILCs) further contributes to the chronic inflammatory response and directly activates adaptive immune cells, including T and B cells. However, development of new tools and model systems is still needed to further understand the chronicity of this inflammatory response and which specific factors are necessary or sufficient to drive CRS pathogenesis. Such studies will be critical for the development of improved therapeutic strategies aimed at treating this highly prevalent and costly disease.

Keywords: Adaptive immunity; Chronic inflammation; Chronic rhinosinusitis; Epithelial cells; Innate immunity.

Fig. 1

Mechanisms of inflammation associated with CRS. 1 A defective epithelial barrier likely plays a critical role in the initiation and maintenance of chronic inflammation in CRS. These defects include reduced secretion of innate host defense molecules and loss of the airway epithelial barrier, along with decreased mucociliary clearance. 2 This in turn may result in increased colonization by S. aureus and, in some cases, fungi. 3 As a result, there is a local accumulation of PAMPS, and other antigens and/or allergens, in the sinonasal cavity that can easily access the underlying mucosal tissues through the defective epithelial barrier. 4 Altogether, this results in the activation of innate effector immune cells (eosinophils, mast cells, ILC2s, etc.) and recruitment and activation of adaptive effector immune cells (T and B cells) to the tissue mucosa