Related Experiment Video
Updated: Jul 25, 2026
Following in Real Time the Impact of Pneumococcal Virulence Factors in an Acute Mouse Pneumonia Model Using Bioluminescent Bacteria
Published on: February 23, 2014
S100A9 is indispensable for survival of pneumococcal pneumonia in mice
Lena Ostermann1, Benjamin Seeliger2,3, Sascha David4
1Division of Experimental Pneumology, Hannover Medical School, Hannover, Germany.
Abstract:
S100A8/A9 has important immunomodulatory roles in antibacterial defense, but its relevance in focal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) is understudied. We show that S100A9 was significantly increased in BAL fluids of patients with bacterial but not viral pneumonia and correlated with procalcitonin and sequential organ failure assessment scores. Mice deficient in S100A9 exhibited drastically elevated Zn2+ levels in lungs, which led to bacterial outgrowth and significantly reduced survival. In addition, reduced survival of S100A9 KO mice was characterized by excessive release of neutrophil elastase, which resulted in degradation of opsonophagocytically important collectins surfactant proteins A and D. All of these features were attenuated in S. pneumoniae-challenged chimeric WT→S100A9 KO mice. Similarly, therapy of S. pneumoniae-infected S100A9 KO mice with a mutant S100A8/A9 protein showing increased half-life significantly decreased lung bacterial loads and lung injury. Collectively, S100A9 controls central antibacterial immune mechanisms of the lung with essential relevance to survival of pneumococcal pneumonia. Moreover, S100A9 appears to be a promising biomarker to distinguish patients with bacterial from those with viral pneumonia. Trial registration: Clinical Trials register (DRKS00000620).
Insights
S100A9 protein is crucial for controlling lung bacterial infections, particularly pneumococcal pneumonia. Its deficiency leads to increased zinc, bacterial growth, and reduced survival, highlighting its role in immune defense.
Area of Science:
- Immunology
- Microbiology
- Pulmonology
Background:
- S100A8/A9 protein's immunomodulatory roles are known, but its specific function in Streptococcus pneumoniae (S. pneumoniae) pneumonia is unclear.
- Bacterial pneumonia diagnosis can be challenging, necessitating biomarkers for differentiation from viral causes.
Purpose of the Study:
- To investigate the role of S100A9 in the host defense against S. pneumoniae.
- To evaluate S100A9 as a potential biomarker for bacterial pneumonia.
Main Methods:
- Analysis of S100A9 levels in bronchoalveolar lavage (BAL) fluids from pneumonia patients.
- Phenotypic analysis of S100A9 knockout (KO) mice challenged with S. pneumoniae.
- Assessment of lung injury, bacterial load, and survival in mouse models.
- Chimeric mouse studies and therapeutic interventions with modified S100A8/A9 protein.
Main Results:
- S100A9 levels were elevated in bacterial pneumonia patients, correlating with procalcitonin and SOFA scores.
- S100A9 KO mice showed increased lung zinc, impaired bacterial clearance, and reduced survival.
- Neutrophil elastase-mediated degradation of collectins (SP-A, SP-D) contributed to reduced survival in S100A9 KO mice.
- Therapy with a stabilized S100A8/A9 protein improved outcomes in S. pneumoniae-infected S100A9 KO mice.
Conclusions:
- S100A9 plays a critical role in antibacterial immunity in the lungs, essential for survival during pneumococcal pneumonia.
- S100A9 is a potential biomarker for distinguishing bacterial from viral pneumonia.
More Related Videos
Related Concept Videos
01:14Atypical Pneumonia
01:25Clinical Significance of Antibiotic Resistance