Infection and Immunity· 2026Q1
Flagellin enhances innate immune responses in human airway epithelium during bacterial infection
- 2citations
- Q1SCImago
- 2026year
Short summary
Apical flagellin administration activates human airway epithelial cells (including those from COPD/CF patients) via TLR5, triggering cytokine production, leukocyte chemotaxis, neutrophil recruitment, and antimicrobial defense pathways, as shown by RNA sequencing in an air-liquid interface model.
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Key points
- Apical flagellin administration activates TLR5-mediated immune signaling in human airway epithelial cells.
- Induced immune responses include cytokine production, leukocyte chemotaxis, neutrophil recruitment, and antimicrobial defense.
- These effects were observed in airway epithelium from healthy individuals, COPD patients, and CF patients.
- Flagellin activated immune responses during infection with Pseudomonas aeruginosa and Streptococcus pneumoniae.
- Epithelial activation alone was insufficient to directly limit bacterial colonization or replication.
AI-generated from the title and abstract; the full text is not read.
Abstract
ABSTRACT Bacterial pneumonia poses a significant challenge to public health, often leading to antibiotic treatment failure. Enhancing innate immunity represents a promising adjunctive strategy to conventional antibiotic therapy. Bacterial flagellin, a Toll-like receptor 5 (TLR5) agonist, has been shown to stimulate innate immune defenses when delivered via the respiratory route, demonstrating efficacy in both preventing and treating bacterial pneumonia in murine models. This protective effect is primarily mediated through TLR5-driven activation of airway epithelial cells. This study aimed to characterize the immunomodulatory effects of flagellin on human primary respiratory epithelium. Using the MucilAir air-liquid interface model and RNA sequencing, we demonstrated that apical administration of flagellin induced robust immune responses in airway epithelium derived from healthy individuals, as well as patients with chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). TLR5-mediated epithelial signaling triggered key immune-related pathways, including cytokine production, leukocyte chemotaxis, neutrophil recruitment, and antimicrobial defense, with strong commonalities across healthy and diseased airway epithelia. Furthermore, we demonstrated that flagellin effectively activated immune responses during infection of the airway epithelium with the bacteria Pseudomonas aeruginosa or Streptococcus pneumoniae . However, epithelial activation alone was insufficient to directly limit bacterial colonization or replication, highlighting the potential role of epithelial-immune cell interactions in achieving effective bacterial clearance. These findings support TLR5 activation as a promising therapeutic strategy to enhance host defense mechanisms and improve treatment outcomes for bacterial pneumonia in both healthy individuals and patients with COPD or CF.
The authors' abstract, as published at the source. Infection and Immunity, 2026 · DOI ↗
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ImmunologyImmunology and Microbiology