(Vienna, 02-07-2025) A recent study led by Philipp Starkl from MedUni Vienna shows that mast cells can influence the behaviour of macrophages in a previously unknown way. The research provides new insights into the interactions of these immune cells in inflammatory processes and immune defence, and lays the foundation for the development of new immunomodulatory therapeutic strategies. The findings have been published in the Journal of Allergy and Clinical Immunology.
Mast cells and macrophages are immune cells that often reside in close proximity in barrier organs such as the skin, lungs and intestines. While macrophages are known for their role as "scavenger cells" and ability to switch between pro- and anti-inflammatory states, the biological functions of mast cells are less well researched. In contrast, mast cells are "notorious" for their key role in allergic reactions and the associated negative effects on the organism. "Due to the spatial proximity of mast cells and macrophages in many different tissues of the body, our study investigated whether and to what extent the substances produced by mast cells during an allergic reaction influence the functionality of macrophages," says study leader Philipp Starkl (Department of Medicine I, MedUni Vienna) about the starting point of the research.
Mast cells influence inflammatory responses of macrophages
Using cell culture models, the researchers were able to demonstrate that mast cell mediators lead to profound changes in the epigenetic, genetic and metabolic configuration of macrophages. Macrophages exposed to these mediators showed changes in oxygen consumption and the production of ATP, the central energy carrier in cells. In addition, epigenetic modifications were identified that could play an important role in the altered macrophage function. One of the most important observations made by the research team was that macrophages which had been "reprogrammed" by mast cells exhibited increased phagocytosis activity and released significantly more pro-inflammatory signalling molecules after contact with bacterial components such as lipopolysaccharide (LPS). "In the mouse model, we were also able to show that the macrophages altered by mast cell messenger substances have a direct effect on inflammatory reactions and can significantly influence the course of a bacterial infection," says first author Dorothea Holter.
The results illustrate the great potential of mast cells to influence the character and function of macrophages. Communication between the two cell types could play an important role in various situations where the efficient but balanced function of macrophages is crucial, such as defence against microbial pathogens or repair of damaged tissue. The new findings could therefore contribute to the development of new immunomodulatory strategies.
Publication: Journal of Allergy and Clinical Immunology
Mast cells activated in vitro can modulate macrophage polarization and antibacterial responses.
Dorothea B. Holter, Sophie Zahalka, Jessica Brösamlen, Mariem Radhouani, Martin L. Watzenboeck, Tyler J. Artner, Asma Farhat, Riem Gawish, Karin Lakovits, Anastasiya Hladik, Federica Quattrone, Wolfgang Weninger, Thomas Krausgruber, Shane J.F. Cronin, Shweta Tikoo, Rohit Jain, Sylvia Knapp, Nikolaus Fortelny and Philipp Starkl*.
DOI: 10.1016/j.jaci.2025.02.040
The study was conducted at the Medical University of Vienna in close collaboration with Sylvia Knapp's research group (Department of Medicine I, MedUni Vienna). Additional support was provided by Shweta Tikoo and Rohit Jain (Department of Dermatology, MedUni Vienna) as well as Shane Cronin (Clinical Department of Laboratory Medicine, MedUni Vienna) and Thomas Krausgruber (Institute of Artificial Intelligence, MedUni Vienna). Essential bioinformatic analyses were performed by Nikolaus Fortelny at the University of Salzburg.