The role of innate immunity in the pathogenesis of chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory condition with a multifactorial basis. Infectious triggers of CRS have been proposed, but demonstration remains elusive. Evolving research suggests that abnormal host mucosal immune responses, rather than specific pathogens themselves, may underlie the chronic inflammatory state. Despite constant contact with airborne particulates and microorganisms, the sinonasal epithelium maintains mucosal homeostasis through innate and adaptive immune mechanisms that eliminate potential threats. Innate immunity encompasses a broad collection of constitutive and inducible processes that can be nonspecific or pathogen directed. Some innate immune pathways are closely intertwined with tissue growth and repair. The persistent inflammation observed in CRS may result from a pathologic imbalance in innate immune interactions between the host and the environment. Impairment of critical innate immune protection renders the sinonasal mucosal surface susceptible to colonization and potential injury, stimulating the prominent adaptive immune response that characterizes CRS.

Figure 1

Innate immunity of the sinonasal tract. The primary mechanism of sinonasal innate immune defense is orderly mucociliary clearance. The mucus blanket, which contains many secreted antimicrobials and opsonins, is continuously propelled to the nasopharynx, providing constitutive, nonspecific protection of the sinonasal mucosal surface. In addition, sinonasal epithelial cells actively participate in innate immunity, using pattern-recognition receptors to detect luminal pathogens and responding directly with selective expression of targeted antimicrobial effectors. At the same time, epithelial cells signal to adaptive immune cells through cytokines and costimulatory molecules to coordinate a vigorous defense of the mucosal surface. Emerging evidence suggests that predominance of certain T-helper (Th) populations (Th1, Th2, and Th17) in the mucosa, as well as the presence of T-regulatory cells (Tregs) may play a role in chronic rhinosinusitis pathogenesis. Epithelial cells guide the recruitment of adaptive immune cells by producing signaling molecules that interact locally with resident dendritic cells and T cells. Cytokines produced by specific T-cell subclasses modulate the innate immune responses of epithelial cells by influencing the pattern of antimicrobial gene expression. Chronic sinonasal inflammatory disease may result from the loss of mucosal homeostasis due to dysregulation of these innate immune pathways.