A recent publication involving researchers from the DZL partner site BREATH provides new insights into the role of the alarmin S100A8 in pulmonary immune defense. Published in the Journal of Infectious Diseases, the study demonstrates that the absence of S100A8 significantly impairs host defense against Streptococcus pneumoniae, thereby negatively affecting the course and severity of bacterial pneumonia.
Bacterial pneumonia, particularly when caused by pneumococci, remains one of the most common severe respiratory infections worldwide. While members of the S100 protein family—especially S100A9—are already recognized as important mediators of innate immunity, the specific role of S100A8 in lung tissue has so far remained insufficiently characterized. This is precisely where the current study provides new insights.
“The aim of our study was to clarify the functional relevance of S100A8 in bacterial lung infections and to better understand the mechanisms underlying impaired local immunity,” explains BREATH scientist Dr. Lena Ostermann. To address this question, the researchers combined experimental pneumococcal infections in S100A8-deficient mouse models with analyses of bronchoalveolar samples from patients with pneumonia.
The findings revealed a clear pattern: in the absence of S100A8, bacterial clearance in lung tissue was markedly reduced. At the same time, increased recruitment of neutrophil granulocytes was observed, accompanied by interstitial and alveolar edema as well as more pronounced tissue damage. Mechanistically, the team identified neutrophil elastase-dependent degradation of the surfactant proteins SP-A and SP-D, which normally play a key protective role in the lung. Their inactivation weakens the alveolar barrier and promotes persistence of the pathogens.
Clinical samples likewise showed altered S100A8/A9 levels that correlated with disease severity. These findings expand the current understanding of alveolar immune regulation and position S100A8 as an important modulator balancing effective pathogen defense and inflammation-induced lung injury. Particularly noteworthy was the observation that administration of recombinant S100A8/A9 proteins significantly improved disease outcomes in the mouse model, highlighting potential therapeutic opportunities.
“Our data suggest that S100A8 could serve not only as a biomarker for improved characterization of bacterial pneumonia, but also as a potential therapeutic target for selectively modulating pulmonary immune responses,” emphasizes Prof. Ulrich Maus, head of the Experimental Pneumology research group and BREATH PI. “In the long term, we see great potential to further refine diagnostic strategies, for example to better distinguish between bacterial and viral pneumonia, and to develop individualized treatment approaches. This could contribute substantially to improving care for patients with severe pneumonia and acute respiratory distress syndrome (ARDS),” adds PD Dr. Benjamin Seeliger, senior physician for intensive care medicine and pneumology at Hannover Medical School.
Original publication: Ostermann L, Seeliger B, Peukert K, Steinmetz LK, Flasche C, Maus R, Stolper J, Vogl T, Pich A, Bode C, Neumann K, Brand K, Tessier PA, Roth J, Maus UA. Lack of S100A8 impairs lung protective immunity against Streptococcus pneumoniae. J Infect Dis. 2025 Dec 26:jiaf647. doi: 10.1093/infdis/jiaf647. Epub ahead of print. PMID: 41456938.
Source: BREATH
