AUTHOR=Kornstädt Lisa , Pierre Sandra , Weigert Andreas , Ebersberger Stefanie , Schäufele Tim J. , Kolbinger Anja , Schmid Tobias , Cohnen Jennifer , Thomas Dominique , Ferreirós Nerea , Brüne Bernhard , Ebersberger Ingo , Scholich Klaus 

TITLE=Bacterial and Fungal Toll-Like Receptor Activation Elicits Type I IFN Responses in Mast Cells

JOURNAL=Frontiers in Immunology

VOLUME=Volume 11 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.607048

DOI=10.3389/fimmu.2020.607048

ISSN=1664-3224

ABSTRACT=Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that during resolution of inflammation mast cells are located in a predominantly antiinflammatory microenvironment. Fittingly, cytokine screening of inflamed tissues showed a downregulation of antiinflammatory and pro-angiogenic cytokines in mast cell-deficient mice. In addition, macrophages in these mice had a decreased ability to phagocytose zymosan and neutrophils. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which has been shown to enhance phagocytosis by macrophages. Bone marrow-derived mast cells released IFN-β in response to zymosan and lipopolysaccharides (LPS). Accordingly, IFN- was detected in mast cells during the resolution phase of the zymosan-induced inflammation. As previously described for macrophages the release of type I IFNs from mast cells depends on internalization and endosome acidification. In conclusion, mast cells produce IFN-β in response to non-viral TLR stimuli and have the potential to influence the phagocytosing activity of macrophages by a variety of antiinflammatory mediators.