Neutrophil recruitment by allergens contribute to allergic sensitization and allergic inflammation

Abstract

Purpose of review: To discuss the presence and role of neutrophils in asthma and allergic diseases, and outline the importance of pollen and cat dander-induced innate neutrophil recruitment in induction of allergic sensitization and allergic inflammation.

Recent findings: Uncontrolled asthma is associated with elevated numbers of neutrophils, and levels of neutrophil-attracting chemokine IL-8 and IL-17 in bronchoalveolar lavage fluids. These parameters negatively correlate with lung function. Pollen allergens and cat dander recruit neutrophils to the airways in a toll-like receptor 4, myeloid differentiation protein-2, and chemokine (C-X-C motif) receptor (CXCR) 2-dependent manner. Repeated recruitment of activated neutrophils by these allergens facilitates allergic sensitization and airway inflammation. Inhibition of neutrophil recruitment with CXCR2 inhibitor, disruption of toll-like receptor 4, or small interfering RNA against myeloid differentiation protein-2 also inhibits allergic inflammation. The molecular mechanisms by which innately recruited neutrophils contribute to shifting the airway inflammatory response induced by allergens from neutrophilic to an eosinophilic-allergic is an area of active research.

Summary: Recent studies have revealed that neutrophil recruitment is important in the development of allergic sensitization and inflammation. Inhibition of neutrophils recruitment may be a strategy to control allergic inflammation.

Figure 1. Schematic diagram showing allergen-induced innate neutrophil recruitment is critical for induction of allergic sensitization and airway inflammation

Recognition of pollens and cat dander by MD2 in the context of TLR4 activates NF-κB mediated secretion of CXCL1, CXCL2, and CXCL8 from the airway epithelium. These chemokines recruit ROS-generating neutrophils to the epithelium via CXCR2. The neutrophil-activated airway epithelium secretes TSLP and IL-33 upon subsequent contact with the same allergens, thereby facilitating allergic sensitization and allergic airway inflammation. ROS; Reactive oxygen species