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

Andrea I Boyd1,2, Leah A Kafer1,2, Isabel F Escapa1

  • 1Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas, USA.

Insights

Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae may increase infection risk, while Dolosigranulum species indicate health. Human nasal organoids model these host-microbe interactions.

Area of Science:

  • Microbiology
  • Immunology
  • Host-Microbe Interactions

Background:

  • Nasal colonization by Staphylococcus aureus or Streptococcus pneumoniae is linked to higher infection risk.
  • Conversely, nasal colonization by Dolosigranulum species is associated with a healthy state.

Purpose of the Study:

  • To investigate host-microbe dynamics in the human nasal mucosa using a novel organoid model.
  • To compare the effects of colonizing human nasal organoids (HNOs) with Staphylococcus aureus, Streptococcus pneumoniae, and Dolosigranulum pigrum.

Main Methods:

  • Human nasal epithelial organoids (HNOs) were monocolonized with S. aureus, S. pneumoniae, or D. pigrum for up to 48 hours.
  • Bacterial localization, cytotoxicity, and host cytokine responses were analyzed.
  • Chemokine expression (CXCL10, CXCL11) was measured.

Main Results:

  • HNOs successfully supported monocolonization, with bacteria localized to the mucus layer and minimal cytotoxicity.
  • Nasal epithelium exhibited species-specific and general cytokine responses, but not type I interferons, indicating colonization rather than infection.
  • Live S. aureus induced IL-1 family cytokines, suggesting inflammasome activation.
  • D. pigrum and live S. aureus decreased CXCL10, while S. pneumoniae increased CXCL11.

Conclusions:

  • Human nasal epithelial organoids serve as a valuable model for studying host-microbe dynamics in the nasal mucosa.
  • The study reveals distinct host responses to colonization by different bacterial species, including inflammatory signaling and chemokine modulation.

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