Innate responses to pollen allergens

Abstract

Purpose of review: The aim of the present review was to discuss the effects of pollen components on innate immune responses.

Recent findings: Pollens contain numerous factors that can stimulate an innate immune response. These include intrinsic factors in pollens such as nicotinamide adenine dinucleotide phosphate oxidases, proteases, aqueous pollen proteins, lipids, and antigens. Each component stimulates innate immune response in a different manner. Pollen nicotinamide adenine dinucleotide phosphate oxidases induce reactive oxygen species generation and recruit neutrophils that stimulate subsequent allergic inflammation. Pollen proteases damage epithelial barrier function and increase antigen uptake. Aqueous pollen extract proteins and pollen lipids modulate dendritic cell function and induce Th2 polarization. Clinical studies have shown that modulation of innate immune response to pollens with toll-like receptor 9- and toll-like receptor 4-stimulating conjugates is well tolerated and induces clear immunological effects, but is not very effective in suppressing primary clinical endpoints of allergic inflammation.

Summary: Additional research on innate immune pathways induced by pollen components is required to develop novel strategies that will mitigate the development of allergic inflammation.

FIGURE 1

Two-signal hypothesis of pollen-induced allergic inflammation. ROS generated by the pollen NADPH oxidases causes GSSG or 4-HNE production and DNA damage. GSSG, 4-HNE, and DNA damage induce the production of interleukin-8, a proinflammatory cytokine that attracts and activates neutrophils. Activated neutrophils also generate ROS. Pollen NADPH oxidase-mediated oxidative stress induces mitochondrial ROS generation. These ROS mediated by innate signaling pathways ‘signal 1’ promote the allergic inflammation ‘signal 2’, the classical allergic inflammation pathway. APC, antigen-presenting cell; 4-HNE, 4-hydroxynonenal; GSSG, oxidized glutathione; ROS, reactive oxygen species; SOD, superoxide dismutase.

FIGURE 2

Proteases in pollens degenerate the epithelial tight and adherence junction. Pollen protease increases the permeability of the airway epithelium by disruption of tight and adherence junction. Pollen allergens can go through airway epithelium easily because of the loss of epithelial barrier function. JAM, junctional adhesion molecules; ZO-1, zonula occludens-1.

FIGURE 3

Neutrophil recruitment by pollens is important for induction of allergic inflammation. Pollen allergen activates nuclear factor-κB, leading to the production of CXCL8 in airway epithelium. Activated neutrophils recruited by CXCL-8 facilitate subsequent allergic inflammation by releasing MMP-9, neutrophil elastase, α-defensins, TGF-β1, and ROS. 4-HNE, 4-hydroxynonenal; GSSG, oxidized glutathione; MMP-9, matrix metalloproteinase 9; ROS, reactive oxygen species; TGF-β1, transforming growth factor beta 1.