Background

Experimental studies suggest that neutrophils could contribute to allergic asthma pathogenesis, mainly driven by a type 2 immune response. Inhalation of diesel exhaust particles (DEP) is implicated in the development and exacerbation of asthma. Combined exposure to DEP and house dust mite (HDM) in vivo induces an increase in eosinophils and neutrophils in bronchoalveolar lavage fluid (BALF).

Aims

We aimed to characterize neutrophilic responses in a subacute and chronic murine model of DEP-aggravated allergic asthma.

Methods

C57BL/6J mice were intranasally exposed to saline, DEP alone, HDM alone or combined HDM+DEP for 3 weeks (subacute) or 6 weeks (chronic). The inflammatory responses were assessed in BALF and lung tissue by flowcytometry and immunohistochemical staining, respectively. Several markers associated with neutrophil migration and activity were examined.

Results

Subacute exposure to HDM+DEP in mice induced a strong mixed eosinophilic/neutrophilic inflammation in BALF and lung and was associated with higher expression of neutrophil-attracting chemokines (CXCL1, CXCL2 and CXCL5) and NET formation compared to sole exposures. After chronic HDM+DEP exposure, a similar neutrophilic response was observed, however the NET formation was less pronounced. Interestingly, the increase of BALF eosinophils was also significantly attenuated after chronic HDM+DEP exposure compared to subacute exposure, suggesting a decreased type 2 airway inflammation.

Conclusion

Our data suggest a role for neutrophils and NETs in pollutant-aggravated eosinophilic allergic asthma. Further research is needed to address whether neutrophils or their mediators could be a possible therapeutic target.