Abstract
Mast cells (MCs) constitute an essential cell lineage that participates in innate and adaptive immune responses and whose phenotype and function are influenced by tissue-specific conditions. Their mechanisms of activation in type I hypersensitivity reactions have been the subject of multiple studies, but the signaling pathways behind their activation by innate immunity stimuli are not so well described. Here, we review the recent evidence regarding the main molecular elements and signaling pathways connecting the innate immune receptors and hypoxic microenvironment to cytokine synthesis and the secretion of soluble or exosome-contained mediators in this cell type. When known, the positive and negative control mechanisms of those pathways are presented, together with their possible implications for the understanding of mast cell-driven chronic inflammation. Finally, we discuss the relevance of the knowledge about signaling in this cell type in the recognition of MCs as central elements on innate immunity, whose remarkable plasticity converts them in sensors of micro-environmental discontinuities and controllers of tissue homeostasis.
Highlights
The immune system (IS) has been defined as a distributed and autonomous entity, since it is composed of many distinct and numerous cells and seems to react without an apparent director [1].one of the main design principles of the IS refers to the dynamic engagement of different cells, which act only briefly and are replaced by others that respond to the new microenvironment [2]
The authors described that the antimicrobial peptide cathelicidin (LL-37) can modify Toll-Like Receptors (TLRs) expression and distribution [37], suggesting that other external stimulus or environmental factors could modify the expression and location of these receptors, thereby altering mast cells (MCs)’ innate response. Another receptor of the IL-1 superfamily has been recently described in MCs. This suppressor of tumorigenicity 2 (ST2) receptor shares most of the signaling system of the TLRs, it is activated by IL-33, an alarmin that is produced in response to infection or injury [38]
Using different human mast cell lines, LTA [35], PGN [35,84] and Pam3CSK4 [83] resulted in robust extracellular signal-regulated kinase (ERK) phosphorylation [35], while in bone marrow-derived mast cells (BMMCs), the latter induced ERK activation in a TLR2and MyD88-dependent manner, an effect that was shown to be essential for eicosanoid production [85]
Summary
The immune system (IS) has been defined as a distributed and autonomous entity, since it is composed of many distinct and numerous cells and seems to react without an apparent director [1]. Cells 2020, 9, 2411 the environment, MCs have been called the sentinels of innate immunity, executing rheostatic functions [6,7,8] They are better known by their role on allergic responses, research performed during the last twenty-five years has clarified its involvement in innate immunity. We present the recent evidence regarding to the description of the main signal transduction pathways that connect innate immunity receptors to the secretion of soluble or exosome-contained pro-inflammatory mediators by MCs, making emphasis in the participation of canonical molecules with distinctive functions on this cell type, the mechanisms of negative control of PRR activation and the effect of environmental conditions, such as hypoxia, on MC signaling
Sign-in/Register to view highlights & summary 
Published Version (
Free)
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 call