Bacterial pneumonia caused by pneumococci is among the most common causes of severe respiratory infections worldwide. Previous studies had already established that members of the S100 protein family, particularly S100A9, play key roles in innate immune defense. However, the specific role of S100A8 in lung tissue has remained unclear. This is precisely where the current study comes in. “The aim of our study was to clarify the functional relevance of S100A8 in the context of bacterial lung infections and to better understand the mechanisms underlying impaired local immunity,” explains BREATH scientist Dr. Lena Ostermann. To this end, the researchers combined experimental pneumococcal infections in S100A8-deficient mouse models with the analysis of bronchoalveolar samples from patients with pneumonia.

The experimental data reveal a clear pattern: in the absence of S100A8, bacterial clearance in lung tissue is markedly reduced. At the same time, there is pronounced neutrophilic infiltration associated with interstitial and alveolar edema as well as increased structural tissue damage. Mechanistically, the authors identified a neutrophil elastase–dependent degradation of the surfactant-associated proteins SP-A and SP-D. These normally protective factors are thereby inactivated, further promoting pathogen persistence and weakening the alveolar barrier function.

In parallel, altered levels of S100A8/A9 were also observed in clinical samples, correlating with disease severity. These findings expand the current understanding of alveolar immune regulation and position S100A8 as a key modulator balancing effective pathogen defense and inflammatory lung injury. Notably, administration of recombinant S100A8/A9 proteins in the mouse model significantly improved clinical outcomes, pointing to potential therapeutic strategies.

“Our data show that S100A8 could serve not only as a biomarker for improved characterization of bacterial pneumonia, but also as a potential therapeutic target to specifically modulate the pulmonary immune response,” 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. These could help to sustainably improve patient care in severe pneumonia and also in ARDS,” adds PD Dr. Benjamin Seeliger, Senior Physician for Intensive Care Medicine and Pneumology at MHH.

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.

Text: BREATH/ AB

Photos: MHH/Tom Figiel, privat