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

Abstract

Human nasal microbiota often includes highly pathogenic members, many of which are antimicrobial resistance threats, e.g., methicillin-resistant Staphylococcus aureus and drug-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 . Learning how these microbionts interact with the nasal epithelium and identifying new means to reduce pathobiont colonization are key goals in the field. As a tool to advance this research, we developed human nasal epithelial organoids (HNOs) differentiated at an air-liquid interface 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 important since the epithelium is an instigator of the initial innate immune response to bacteria. Here, we identified differential epithelial cytokine responses to these three bacteria, setting the stage for future research.