Nasal microbionts differentially colonize and elicit cytokines in human nasal epithelial organoids
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Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is associated with an increased risk of infection by these pathobionts, whereas nasal colonization by Dolosigranulum species is associated with health. H uman n asal epithelial o rganoids (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 with 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 S. aureus colonization robustly induced IL-1 family cytokines, suggestive of inflammasome signaling. D. pigrum and live S. aureus decreased CXCL10, whereas S. pneumoniae increased CXCL11, chemokines involved in antimicrobial responses to both viruses and bacteria. Overall, HNOs are a compelling model system to reveal host-microbe dynamics at the human nasal mucosa.
IMPORTANCE
Human nasal microbiota often includes highly pathogenic members, many of which are antimicrobial resistance threats, e.g., methicillin-resistant Staphylococcus aureus and antibiotic-resistant Streptococcus pneumoniae . Preventing colonization by nasal pathobionts decreases infections and transmission. In contrast, nasal microbiome studies identify candidate beneficial bacteria that might resist pathobiont colonization, e.g., Dolosigranulum pigrum . Discovering how these microbionts colonize the human nasal passages and means to reduce pathobiont colonization is limited by previous models. This creates an urgent need for human-based models that exemplify bacterial nasal colonization. We addressed this need by developing human nasal epithelial organoids (HNOs) as a new model system of bacterial nasal colonization. HNOs accurately represent the mucosal surface of the human nasal passages enabling exploration of bacterial-epithelial interactions, which is crucial since the epithelium instigates the initial innate immune response to bacteria. Here, we identified differential epithelial cytokine responses to these three bacteria setting the stage for future research.
