A novel Siglec-F+ neutrophil subset in the mouse nasal mucosa exhibits an activated phenotype and is increased in an allergic rhinitis model.

Neutrophils are important phagocytic cells for host defense against pathogens. They are rapidly recruited to the site of infection, release antimicrobial peptides and cytokines, and engulf and kill microbes. Neutrophils also accumulate in allergic inflammatory sites. Here we characterized neutrophil accumulation in the nasal mucosa using a mouse model of allergic rhinitis, in which mice were sensitized by intraperitoneal injection of ovalbumin (OVA) and then challenged by intranasal administration of OVA or PBS. In the nasal mucosa of both PBS- and OVA-challenged mice, we found a cell subset expressing the eosinophil marker Siglec-F in the Ly-6G+ neutrophil population. Morphological analysis of the sorted Ly-6G+Siglec-F+ cells revealed that they were devoid of eosinophilic granules in the cytosol and were apparently neutrophils, but compared to conventional Ly-6G+Siglec-F- neutrophils, they had a more lobulated, "botryoid" nucleus. Siglec-F+ neutrophils were barely found in the nasopharynx-associated lymphoid tissue, cervical lymph nodes, the spleen, or blood. Both Siglec-F+ neutrophils and conventional neutrophils showed increased numbers in the nasal mucosa of OVA-challenged mice. Compared to conventional Siglec-F- neutrophils, Siglec-F+ neutrophils exhibited an activated phenotype and enhanced effector functions. Taken together, our findings identify Siglec-F+ neutrophils as a novel neutrophil subset with an activated phenotype that resides specifically in the nasal mucosa.