Bacterial and fungal toll-like receptor activation elicits type I IFN responses in mast cells

  • 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 mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-β synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-β was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-β, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.
Author:Lisa KornstädtGND, Sandra Pierre, Andreas WeigertORCiDGND, Stefanie EbersbergerORCiD, Tim J. Schäufele, Anja Kolbinger, Tobias SchmidORCiDGND, Jennifer Cohnen, Dominique Jeanette ThomasORCiDGND, Nerea Ferreirós BouzasORCiDGND, Bernhard BrüneORCiD, Ingo EbersbergerORCiDGND, Klaus Scholich
Parent Title (English):Frontiers in immunology
Publisher:Frontiers Media
Place of publication:Lausanne
Document Type:Article
Date of Publication (online):2021/02/12
Date of first Publication:2021/02/12
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2021/05/25
Tag:IFN-β; inflammation; mast cells; resolution; toll-like receptor
Issue:art. 607048
Page Number:15
First Page:1
Last Page:15
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0