Mast cells activated in vitro can modulate macrophage polarization and antibacterial responses

• DOI: 10.1016/j.jaci.2025.02.040
• Publication Date: 2025-05-26T23:10:17Z
• Authors: Dorothea B. Holter; Sophie Zahalka; Jessica Brösamlen; Mariem Radhouani; Martin L. Watzenb...; 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; Philipp Starkl
• Keywords: Mast (botany); Macrophage polarization

Mast cells and macrophages are tissue-resident immune frequently found in close proximity barrier organs. Macrophages show high plasticity microenvironmental factors, such as cytokines, can influence their phenotype. central allergic reactions where allergens cause mast cell activation via antigen-specific IgE antibodies the release of a multitude inflammatory substances. While have clearly defined physiologic roles tissue maintenance host defense against microbes, biological functions less well defined. In current study, we aimed to understand interplay how cell-released mediators shape macrophage phenotype function. Using primary vitro models combined with microscopic, functional, metabolic, genetic epigenetic analyses, investigate polarization effects produced upon antigen. We apply engraftment strategy explore potential vivo implications cell-mediated priming. find that pre-formed newly-synthesized released by activated different from classical M1/M2 paradigm. Exposure supernatant induces reprogramming macrophages. This profound priming effect strongly alters phagocytosis, cytokine production transcriptomic responses secondary exposure bacteria or products. Importantly, transfer primed also significantly affects outcome sterile inflammation bacterial peritonitis. Our study highlights great directors