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 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.
Highlights
Mast cells are part of the first line of defense of the body, protecting against invading pathogens and other environmental harm
Since in macrophages TLR2- and TLR4-induced IFN-b release depends on the internalization of these receptors, we investigated if receptor internalization is a prerequisite in mast cells [12, 13]
It is well known that many cell types, including mast cells, respond to viral infections through TLR3, TLR7, and TLR9 initiating the type I IFN response as well as release of various proinflammatory cytokines [7, 8], which make them targets for antiinflammatory treatments including the use of cytokines of the IL-1 family with antiinflammatory properties [39, 40]
Summary
Mast cells are part of the first line of defense of the body, protecting against invading pathogens and other environmental harm They are long-lived, tissue-resident leukocytes, located most abundantly close to surfaces exposed to the environment, like skin and mucosal tissues. The precise response and signaling pathway activated in a mast cell depends on the stimulus activating the cell, which can be recognized and discriminated by an extensive repertoire of receptors. These receptors coordinate the selective release of proinflammatory (e.g. histamine, interleukin (IL)-1b) or antiinflammatory (e.g. IL-4, IL-10, IL-13) mediators [1, 3]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
