Language

English

Publication Date

10-29-2025

Journal

mSphere

DOI

10.1128/msphere.00493-25

PMID

41025782

PMCID

PMC12570476

PubMedCentral® Posted Date

9-30-2025

PubMedCentral® Full Text Version

Post-print

Abstract

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. Human nasal epithelial organoids (HNOs) differentiated at air-liquid interface (ALI) physiologically recapitulate human nasal respiratory epithelium with a robust mucociliary blanket. Due to their natural stem-like properties, HNO lines are a long-term experimental resource that offers genetic diversity based on the different donors. To develop HNOs as a new model system for bacterial nasal colonization, we reproducibly monocolonized HNOs differentiated at ALI with S. aureus, S. pneumoniae, or Dolosigranulum pigrum for up to 48 h 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, which is consistent with colonization rather than infection. Only live S. aureus colonization robustly induced epithelial cell production of interleukin-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 new model system for uncovering microbe-epithelial cell dynamics at the human nasal mucosa.

Keywords

Humans, Cytokines, Organoids, Streptococcus pneumoniae, Staphylococcus aureus, Nasal Mucosa, Microbiota, Epithelial Cells, human nasal organoids, HNO, nasal colonization, epithelial innate immune response, bacterial colonization, Dolosigranulum pigrum, Staphylococcus aureus, MRSA, Streptococcus pneumoniae

Published Open-Access

yes

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