Anti-inflammatory role of CD11b+Ly6G+ neutrophilic cells in allergic airway inflammation in mice.

Asthma is a chronic inflammatory disease driven by overactivation of T helper cell type 2 (Th2) responses. In the present study, we investigated the functional relevance of CD11b+Ly6G+ neutrophilic cells in allergic airway inflammation in vivo. Allergic airway inflammation in mice was induced by house dust mite (HDM) or ovalbumin (OVA) sensitization and challenge. CD11b+Ly6G+ neutrophilic cells and T cell phenotypes were quantified by flow cytometry. To assess the functional in vivo relevance, CD11b+Ly6G+ neutrophilic cells were adoptively transferred intravenously or intratracheally and consequences on airway inflammation were studied. Adoptively transferred CD11b+Ly6G+ neutrophilic cells attenuated Th2 and Th17 responses and airway inflammation in vivo. Collectively, our results demonstrate that CD11b+Ly6G+ neutrophilic cells suppress airway inflammation in allergic mice in vivo. Adoptive cellular transfer of suppressive neutrophilic cells may represent an attractive therapeutic strategy for allergic airway inflammation.

Pseudomonas aeruginosa Airway Infection Recruits and Modulates Neutrophilic Myeloid-Derived Suppressor Cells.

Pseudomonas aeruginosa is an opportunistic pathogen that causes infections mainly in patients with cystic fibrosis (CF) lung disease. Despite innate and adaptive immune responses upon infection, P. aeruginosa is capable of efficiently escaping host defenses, but the underlying immune mechanisms remain poorly understood. Myeloid-derived suppressor cells (MDSCs) are innate immune cells that are functionally characterized by their potential to suppress T- and natural killer (NK)-cell responses. Here we demonstrate, using an airway in vivo infection model, that P. aeruginosa recruits and activates neutrophilic MDSCs, which functionally suppress T-cell responses. We further show that the CF gene defect (CF transmembrane conductance regulator, CFTR) modulates the functionality, but not the recruitment or generation of neutrophilic MDSCs. Collectively, we define a mechanism by which P. aeruginosa airway infection undermines host immunity by modulating neutrophilic MDSCs in vivo.