Researchers investigate the physical locations and relationships of immune cells in healthy and inflamed tissues.

In our daily lives, just by eating or breathing, we are constantly exposing our tissues to microbes and particulate matter that can elicit low level inflammatory responses. The impact of this inflammation over time is not well understood.

Mononuclear phagocyte cells (MPs) are key regulators in the inflammatory process. They are present in every tissue and are very diverse with multiple origins. One of the goals in Prof. Andreas Schlitzer’s lab at the Life and Medical Sciences Institute (LIMES) of the University of Bonn, Germany, is to understand the distribution, function and origin of MPs in healthy tissues and during acute or chronic inflammation. His lab is using a multiplex tissue microscopy system with the Akoya Biosciences solution and the ZEISS Axio Observer microscope to characterize the physical locations and relationships of immune cells in these tissues.

Although there were several options in the market, we selected the ZEISS Axio Observer microscope to integrate with the Akoya Biosciences solution as it offered the best sensitivity and an optimal speed of acquisition. We can acquire the full left murine lung stained with 40 antibodies in less than 32 hours.

In another project, they are studying the effect of low-grade inflammation in the lung. After stimulation, there is a rapid and pronounced influx of a subpopulation of alveolar macrophages that have a pro-inflammatory profile that is kept for several weeks and enhances the response to subsequent challenges. Interestingly, when pulmonary fibrosis is induced in mice that had been stimulated, the disease progression is slower and survival rates improve. Besides doing a detailed characterization of these cells and the genes controlling this phenotype, they used a 40-plex CODEX antibody panel to visualize the lung architecture and determine if major structural changes occur.

In agreement with their flow cytometry analyses, the images showed an increase of monocytes and monocyte-derived alveolar macrophages. They also revealed the absence of major structural changes. Nonetheless, in the aerial spaces, such as bronchioles, infiltrates of cells were observed. These infiltrates were composed predominantly of the macrophage/monocyte populations they had identified, but also other myeloid cells and even lymphoid cells were present.

We would like to exploit the high dimensionality of multiplex tissue microscopy to study the diversity of myeloid cells in multiple tissues and identify non-described tissue-specific populations. There is so much we still don’t understand and we see great potential in leveraging such findings to eventually lead to new and better targeted treatments for multiple health conditions.