Nasal microbionts differentially colonize and elicit cytokines in human nasal epithelial organoids.

Nasal colonization by or is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by species is associated with health. Human nasal epithelial organoids (HNOs) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. We reproducibly monocolonized HNOs with these three bacteria for up to 48 hours with varying kinetics across species. HNOs tolerated bacterial monocolonization with localization of bacteria to the mucus layer and minimal cytotoxicity compared to uncolonized HNOs. Human nasal epithelium exhibited both species-specific and general cytokine responses, without induction of type I interferons, consistent with colonization rather than infection. Only live colonization induced IL-1 family cytokines, suggestive of inflammasome signaling. and live decreased CXCL10, whereas increased CXCL11, chemokines involved in antimicrobial responses. HNOs are a compelling model system to reveal host-microbe dynamics at the human nasal mucosa.