Immune surveillance of the nasal mucosa by neutrophils 4548

Abstract Description The nasal cavity serves as a critical barrier, filtering airborne pathogens to prevent them from reaching the lungs. Immune cells in the nasal mucosa neutralize these pathogens, protecting against local infection. However, the composition, origins, and functions of these immune populations remain largely unexplored. Our research identified a significant population of extravascular neutrophils (EVNs) in the nasal mucosa during homeostasis. Using cell surface markers and mRNA profiles, these EVNs were categorized into three subsets: N1, N2, and N3. Through parabiosis and imaging, we found that N1 neutrophils reside in bone marrow adjacent to the nasal cavity and likely migrate directly into the mucosa via bone conduits. By contrast, N2 neutrophils are derived from the bloodstream and differentiate into N3 neutrophils within 5–6 days. Functionally, N2 neutrophils express genes characteristic of conventional neutrophils and are the primary subset responsible for pathogen phagocytosis. Meanwhile, N3 neutrophils upregulate genes associated with antigen-presenting cells, engulf material from surrounding cells under steady-state conditions, and present antigens to CD8+ T cells in vitro. In summary, the nasal mucosa harbors a diverse population of EVNs with distinct origins, phenotypes, and specialized functions. These findings highlight the complexity of the nasal immune landscape and its essential role in host defense. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)