Constitutive immune surveillance of the nasal mucosa by neutrophils

Abstract

Abstract The nasal mucosa is a versatile tissue where functions such as olfaction and conditioning of air take place. A particularly relevant and less explored function of this tissue relates to its capacity to respond to insult. Air-borne pathogens can use the nasal mucosa as a portal of entry to further disseminate into deeper tissues and little is known about the immune cell populations these pathogens encounter upon infection. We asked what immune cell populations are present in the murine nasal mucosa and unexpectedly found extravascular neutrophils to be a constitutive and prominent population in the steady state. These neutrophils were found in comparable numbers in conventional vs. germ-free mice and can be divided into three well-defined populations based on the expression of specific cell surface markers and mRNA transcript profiles. One of the populations was traced to nasal mucosa-associated pockets of bone marrow and determined to contribute to the nasal mucosa neutrophil extravascular pool. A second population was found to preferentially phagocytose bacteria during infection. In the absence of infection, this population differentiates into a third population, which interacts with other cells of the nasal mucosa in a manner that resembles trogocytosis. Lastly, we found extravascular granulocyte hematopoietic precursors in the nasal mucosa that likely contribute to the extravascular neutrophil pool. Thus, the nasal mucosa encompasses a constitutive population of extravascular neutrophils that show diverse origins and specialization of function. These findings contribute to our understanding of the composition and development of the microenvironment that air-borne pathogens encounter upon infection in the nasal mucosa.