Role of the neutrophil in a mouse model of pollutant-aggravated allergic asthma

Diesel exhaust particles (DEP) have been proven to worsen asthma. We demonstrated that combined exposure to house dust mite (HDM) and DEP in vivo in mice increases both eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF) compared to sole exposures and also results in higher levels of neutrophil-recruiting chemokines and neutrophil extracellular traps (NETs) (PMID: 37105460). We aimed to unravel whether neutrophils modulate the DEP-aggravated eosinophilic airway inflammation. First, we monitored the airway inflammatory cell dynamics upon intranasal exposure to HDM+DEP in a 3-week model, by analyses at multiple time points after last exposure. BALF neutrophils were highest at 24 hours after last HDM+DEP exposure and decreased at later time points, while BALF eosinophils tended to increase with time. This early neutrophilic response associated with high expression of neutrophil-attracting chemokines (CXCL1, 2 and 5) and NET formation. To evaluate whether there is a role for neutrophils in inducing type 2 eosinophilic responses, we interfered with neutrophils and neutrophil elastase in our murine HDM+DEP model by anti-Ly6G and sivelestat administration, respectively. Neutrophils were dramatically reduced after anti-Ly6G administration in BALF, lung and blood -indicating that the depletion was successful- without affecting the eosinophilic inflammation upon HDM+DEP exposure. Sivelestat treatment tended to decrease BALF inflammation, including eosinophils, upon HDM+DEP exposure, but did not affect eosinophilic inflammation in lung tissue. In conclusion, neutrophil interference does not significantly attenuate eosinophilic inflammation in a mouse model of pollutant-aggravated asthma.