Mast cells in the development of adaptive immune responses

Abstract

Mast cells are so widely recognized as critical effector cells in allergic disorders and other immunoglobulin E-associated acquired immune responses that it can be difficult to think of them in any other context. However, mast cells also can be important as initiators and effectors of innate immunity. In addition, mast cells that are activated during innate immune responses to pathogens, or in other contexts, can secrete products and have cellular functions with the potential to facilitate the development, amplify the magnitude or regulate the kinetics of adaptive immune responses. Thus, mast cells may influence the development, intensity and duration of adaptive immune responses that contribute to host defense, allergy and autoimmunity, rather than simply functioning as effector cells in these settings.

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

“…Mast cells have been implicated in the control of bacterial and viral infections, 31,32 immunosurveillance, in disease progression 1,3,30 and, more recently, as intermediaries in regulatory T cell tolerance. 40 However, the role gzmB may play in any of these processes is unknown.…”

“…Recent evidence implicates mast cell-derived gzmB in the inhibition of tumorigenesis. 1,3,10 Mast cell-secreted gzmB may also assist in the control of virus infections by either cleaving viral surface proteins critical for host cell entry, 10 or by inducing anoikis in gzmB-susceptible virus-infected target cells. Mast cell migration and accumulation at sites of viral infections supports this contention.…”

“…[1][2][3] On receiving the appropriate stimuli, mast cells can release three classes of mediators: preformed granule-associated mediators, such as histamine, tryptase, chymase and other proteases; newly generated lipid mediators, that is, leukotrienes and prostaglandins; and a variety of cytokines and chemokines. [1][2][3] In contrast to lipid mediators and cytokines, which have to be synthesized de novo, preformed granuleassociated mediators can be secreted almost without delay after triggering of certain receptors. 1 Recent work on mouse has identified transcripts for the serine proteinase granzyme (gzm) B in cultured naive mast cells.…”

Immunomodulatory mast cells: negative, as well as positive, regulators of immunity

“…Such 'effector functions' of mast cells include killing pathogens 2,3,7 , degrading potentially toxic endogenous peptides [8][9][10] or components of venoms 9,11 , and regulating the numbers, viability, distribution, phenotype or 'non-immune' functions of structural cells, such as fibroblasts and vascular endothelial cells. Mast cells can exert their effector functions through the direct or indirect actions of a wide spectrum of mast-cell-derived products, and such effects can be observed in both innate [1][2][3]12 and acquired 1,5,6,12,13 immune responses (BOX 1).…”

“…Through effector and/or immunomodulatory functions, mast cells can promote the initiation and increase the magnitude of inflammation, tissue remodelling and, in some cases, tissue injury associated with the innate or adaptive immune responses to pathogens, as well as during allergic or autoimmune disorders [1][2][3][5][6][7]13 . Given the many mechanisms by which mast cells can mediate these effects, they are often thought of as cells whose primary role is to 'turn on an immune response'.…”