Rethinking neutrophils and eosinophils in chronic rhinosinusitis

Abstract

Chronic rhinosinusitis (CRS) often is characterized by an eosinophilic inflammatory pattern, nowadays referred to as type 2 inflammation, although the mucosal inflammation is dominated by neutrophils in about a third of the patients. Neutrophils are typically predominant in 50% of patients with CRS without nasal polyps, but also are found to play a role in patients with severe type 2 CRS with nasal polyp disease. This review aims at summarizing the current understanding of the eosinophilic and neutrophilic inflammation in CRS pathophysiology, and provides a discussion of their reciprocal interactions and the clinical impact of the mixed presentation in patients with severe type 2 CRS with nasal polyps. A solid understanding of these interactions is of utmost importance when treating uncontrolled severe CRS with nasal polyps with biologicals that are preferentially directed toward type 2 inflammation. We here focus on recent findings on both eosinophilic and neutrophilic granulocytes, their subgroups and the activation status, and their interactions in CRS.

Keywords: Charcot-Leyden crystals; Chronic rhinosinusitis; IL-17; activation; biologicals; eosinophils; extracellular traps; neutrophils; type 2 inflammation.

Figure 1:

Mixed presence of eosinophils and neutrophils in CRSwNP. Eosinophils (left) and neutrophils (right) in the mucosa of CRSwNP via immunohistochemistry staining of major basic protein (MBP) and elastase, respectively.

Figure 2:

Pathophysiology of a mixed eosinophilic-neutrophilic inflammation in severe type 2 CRSwNP. Both an eosinophilic inflammation (left side) and a neutrophilic inflammation (right side) contribute to the pathophysiology in the mucosa of severe type 2 CRSwNP. Both responses impact the course of the disease and reciprocal interactions between eosinophils and neutrophils contribute to the persistency and severity of the disease. EETs, eosinophil extracellular traps; NETs, neutrophil extracellular traps; CLCs, Charcot-Leyden crystals, MBP, major basic protein; ECP, eosinophil cationic protein; EDN, eosinophil-derived neurotoxin; TSLP, thymic stromal lymphopoietin; RANTES, regulated on activation, normal cell expressed and secreted.