The Role of Innate Immunity in Chronic Rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a clinical syndrome associated with persistent inflammation of the mucosa of the nose and paranasal sinuses. The definition of CRS is intentionally inclusive, encompassing, for example, both the polypoid (CRSwNP) and nonpolypoid (CRSsNP) forms of the disease but does not address causation or etiology. Objective evidence for mucosal inflammation using nasal endoscopy and/or computerized tomography (CT) is required for confirmation of the diagnosis. Historically, CRSsNP was considered to result from an incompletely treated case of acute infectious rhinosinusitis resulting in chronic infection. CRSwNP was considered a distinct, noninfectious disorder of unclear etiology, perhaps related to atopy. Over the last decade, two dominant hypotheses attempted to broadly explain CRS etiology as a response to common intranasal organisms:the Alternaria ‘fungal hypotheses’and staphylococcus aureus ‘superantigen hypotheses’. These current prevailing theories have focused interest on identification of the predominant, presumably microbial, agents inciting CRS rather than searching for a putative defect(s) in the host response. Data confirming either fungi or staphylococci as the primary antigenic or etiologic agent triggering CRS are limited, however, and clinical success with either antifungal or antibiotics has unimpressive. Furthermore, these two classes of organisms can be identified in nasal lumen of a high percentage of normal people without CRS, indicating that disease expression will manifest only in susceptible individuals. From this perspective, CRS may be viewed as analogous toinflammatory bowel disease, where in tolerance mechanisms toward commensal organism are impaired. The shifting emphasis away from environmental and microbial agents toward identifying host susceptibility is well established in other chronic inflammatory disease involving epithelial surfaces such as atopic dermatitis, asthma and inflammatory bowel disease. Theoretically, the primary susceptibility could reside in the host acquired immune system, such as in Tcell subsets for example, but epidemiologic research into CRS suggests that its incidence is not strongly correlated with other inflammatory condition outside the airway, suggesting that susceptibility specific to the airway epithelium is more likely. The respiratory epithelium now is known to be involved in innate immunity. The innate immune system comprises cells and their associated mechanisms that provide the first line of defense against pathogens through genetically encoded pathways with limited specificity for molecular structures. In addition to the physical barrier and pathogen clearing effects of the mucociliary clearance system, sinonasal mucosa has been shown to express a vast arsenal of antimicrobial molecules. Research on the innate immune system over the years had focused on a number of large topics. The first topic was the diverse role of (airway) epithelium in the innate defense. The second topic was the activity of different receptors by which cells can detect the outside environment, and the third was the action of secreted mediators that fight off potential threats.