Exposure of allergic subjects to ragweed pollen in a pollen exposure chamber recruits neutrophils that stimulate IL-33 secretion from airway epithelial cells

Abstract

Challenge of mice with ragweed pollen extract (RWPE) stimulates TLR4-mediated innate neutrophil recruitment. Adoptive transfer of neutrophils into the airways of Tlr4 KO mice reconstitutes RWPE-induced allergic airway inflammation and IL-33 secretion (PMID 26086549). Here we test the hypothesis that exposure of allergic human subjects to ragweed pollen stimulates recruitment of neutrophils that stimulate IL-33 secretion from airway epithelial cells. Ten healthy non-allergic subjects and 18 ragweed allergic responder subjects with allergic rhinitis were exposed to ragweed pollens in a pollen exposure chamber (PEC) for three hours, and allergic symptoms scores were recorded (IRB Protocol Number: 1.2016). Blood neutrophils were isolated from four healthy and four allergic subjects at baseline and at 3h after start of pollen exposure, and cocultured with human bronchial epithelial cells (HBEC) for 24 hours. IL-33 levels were measured in cell supernatants. Exposure of allergic but not healthy non-allergic subjects to ragweed pollen increased naso-ocular symptom scores in 30 mins that peaked at 3 hours, and increased the numbers of blood neutrophils. Culture of neutrophils obtained from allergic and healthy human subjects at baseline stimulated secretion of IL-33 secretion. Neutrophils obtained three hours post ragweed exposure stimulated even greater IL-33 secretion. Exposure of allergic human subjects to ragweed pollen in PEC stimulates neutrophil recruitment into the blood. Neutrophils obtained from subjects after ragweed exposure stimulates greater IL-33 secretion than those obtained at baseline. We suggest that pollen exposure stimulates neutrophil recruitment, and these neutrophils facilitate allergic inflammation by stimulating IL-33 secretion from airway epithelial cells.