Researchers at Leibniz IPHT and Jena University Hospital use light to study how lung immune cells respond to SARS-CoV-2.

How does the lung respond to an infection with the coronavirus? Within the Leibniz Center for Photonics in Infection Research, a team is addressing this question using Raman spectroscopy. This light-based technique makes biochemical changes in individual immune cells visible—without markers and directly in the tissue.

When SARS-CoV-2 enters the lung, alveolar macrophages are among the first immune defense cells to respond. Located in the alveoli, they recognize pathogens, remove cellular debris, and regulate inflammatory processes. The biochemical changes that occur within these cells are still only partly understood. This is the focus of research by Max Naumann, a doctoral researcher in the Clinical Spectroscopic Diagnostics department at Leibniz IPHT, working closely with the research group led by PD Dr. Stefanie Deinhardt-Emmer in Medical Microbiology at Jena University Hospital.

The team studies residual samples of human lung tissue that are removed during transplantation of a “healthy” lung and prepared into slices only a few hundred micrometers thick. In these ex vivo lung slices, both the fine architecture of the lung and the interactions between different cell types are preserved. This allows immune responses to be examined in a controlled experiment without removing the complex tissue from its biological context.

The key technology is Raman spectroscopy. Laser light is directed at individual immune cells; a small portion of the light is scattered back in a way that depends on the cell’s chemical composition. The resulting signals form a spectrum—a chemical fingerprint that provides information about molecules such as RNA, lipids, proteins, and sugars. The advantage of this method is that it requires no stains or markers and does not alter the cells.

The analyses reveal clear differences between macrophages from infected and non-infected lung tissue. In infected samples, changes are observed in RNA content as well as in the cells’ sugar and lipid metabolism. These patterns indicate an activated, inflammatory state. Statistical analyses allow reliable differentiation between cells from the two conditions.

This work demonstrates how photonic methods can be used to analyze immune responses in the lung in greater detail, providing a methodological basis for further diagnostic research.

 

Original Publication: Naumann M, Hornung F, Eiserloh S, et al. Investigating alveolar macrophages in an human ex vivo precision-cut lung slice model of SARS-CoV-2 infection using Raman spectroscopy—A case study. Clin Transl Med. 2025; 15:e70453. https://doi.org/10.1002/ ctm2.70453