Primary human nasal, nasopharyngeal, and bronchial epithelia show distinct immune responses to various pathogens

The respiratory epithelium serves as initial defense against airborne pathogens through its barrier function and induction of immune responses. To study epithelial-pathogen interactions, we used primary epithelial models that closely resembled the epithelia of the airways, for which we collected nasal (n = 7), nasopharyngeal (n = 3), and bronchial (n = 4) epithelial cells from different donors. We cultured these epithelial cells on an air-liquid interface and evaluated their differentiation status. To assess how the different epithelial models respond to distinct types of exposures, the cells were stimulated with IFN-γ, Streptococcus pneumoniae, Neisseria meningitidis, or respiratory syncytial virus (RSV) for 72 h. The nasopharyngeal epithelium was distinct from nasal and bronchial cells with respect to morphology, pathogen load, and induction of cytokine responses, while nasal and bronchial epithelial cells had similar, but not identical cytokine profiles. Each tissue type and stimulus showed specific cytokine patterns. Interestingly, donor-specific differences for IFN-λ2,3 and IL-6 responses were found during meningococcal and RSV infections. Our data highlight morphological differences and a broad variety of epithelial cytokine responses in the different regions of the upper respiratory tract. These different epithelial models will help unravel why some pathogens target specific respiratory regions and why certain individuals are more susceptible to infections.