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Updated: Jun 10, 2026
Sublingual Immunotherapy as an Alternative to Induce Protection Against Acute Respiratory Infections
Published on: August 30, 2014
Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection
Natalia Muñoz1, Laurye Van Maele, Juan M Marqués
1Department of Biotechnology, Instituto de Higiene, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
Abstract:
Streptococcus pneumoniae is a major cause of pneumonia in infants and the elderly. Innate defenses are essential to the control of pneumococcal infections, and deficient responses can trigger disease in susceptible individuals. Here we showed that flagellin can locally activate innate immunity and thereby increase the resistance to acute pneumonia. Flagellin mucosal treatment improved S. pneumoniae clearance in the lungs and promoted increased survival of infection. In addition, lung architecture was fully restored after the treatment of infected mice, indicating that flagellin allows the reestablishment of steady-state conditions. Using a flagellin mutant that is unable to signal through Toll-like receptor 5 (TLR5), we established that TLR5 signaling is essential for protection. In the respiratory tract, flagellin induced neutrophil infiltration into airways and upregulated the expression of genes coding for interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), CXCL1, CXCL2, and CCL20. Using depleting antibodies, we demonstrated that neutrophils are major effectors of protection. Further, we found that B- and T-cell-deficient SCID mice clear S. pneumoniae challenge to the same extent as immunocompetent animals, suggesting that these cell populations are not required for flagellin-induced protection. In conclusion, this study emphasizes that mucosal stimulation of innate immunity by a TLR not naturally engaged by S. pneumoniae can increase the potential to cure pneumococcal pneumonia.
Insights
Flagellin mucosal treatment enhances innate immunity, improving resistance to Streptococcus pneumoniae pneumonia. This TLR5-dependent approach clears bacteria, restores lung tissue, and boosts survival, highlighting a novel therapeutic strategy.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Streptococcus pneumoniae is a primary cause of pneumonia, particularly in vulnerable populations.
- Innate immune defenses are critical for controlling pneumococcal infections, with deficiencies leading to disease susceptibility.
Purpose of the Study:
- To investigate the potential of flagellin, a bacterial component, to activate innate immunity against Streptococcus pneumoniae.
- To determine the role of Toll-like receptor 5 (TLR5) signaling in flagellin-mediated protection against pneumococcal pneumonia.
Main Methods:
- Mucosal administration of flagellin to mice infected with Streptococcus pneumoniae.
- Assessment of bacterial clearance, survival rates, and lung tissue restoration.
- Utilized flagellin mutants deficient in TLR5 signaling and neutrophil-depleting antibodies.
- Evaluated the role of adaptive immunity by using B- and T-cell-deficient SCID mice.
Main Results:
- Flagellin treatment significantly improved Streptococcus pneumoniae clearance and increased survival rates.
- TLR5 signaling was essential for flagellin-induced protection, which involved neutrophil recruitment and upregulation of inflammatory genes (IL-6, TNF-α, CXCL1, CXCL2, CCL20).
- Neutrophils were identified as key mediators of protection, while B and T cells were not required for flagellin-induced immunity.
Conclusions:
- Mucosal stimulation with flagellin effectively enhances innate immune responses against pneumococcal pneumonia.
- This TLR5-dependent strategy promotes bacterial clearance, tissue repair, and survival, offering a promising therapeutic avenue.
- Targeting innate immunity via TLRs not typically engaged by the pathogen represents a novel approach to treating bacterial pneumonia.
