Mast cells in allergy and infection: versatile effector and regulatory cells in innate and adaptive immunity

Abstract

Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and many other stimuli, including products derived from either pathogens or the host during innate immune responses. Although mast cells are best known for their role in IgE-associated allergic disorders, mast cells can also exacerbate models of autoimmunity, enhance the sensitization and/or effector phases of certain cutaneous contact hypersensitivity responses, and increase inflammation and mortality during some severe bacterial infections. In other settings, however, mast cells can limit inflammation and tissue injury: mast cells promote host resistance in certain models of bacterial or parasite infection, limit pathology during some acquired immune responses to environmental Ag, including examples of severe contact hypersensitivity, and have adjuvant-like properties that can enhance the development of protective immunity against pathogens. These and other findings suggest that mast cells occupy a critical niche at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may function to perturb or help to restore homeostasis (or both), with consequences that can either promote health or contribute to disease.

Figure 1. Diverse roles of mast cells in innate or acquired (adaptive) immune responses that contribute to health or disease

Th is figure highlights some of the roles of mast cells that are thought to promote health (green, right) or exacerbate disease (red, left). These functions either have been demonstrated using mast cellengrafted genetically mast cell-deficient mice (*), or mice that lack certain mast cell-associated products (⁺) or IgE^#, or represent speculation (?) based on known properties of mast cells. Arrows link examples of settings in which, depending on the circumstances, mast cells may either promote health or exacerbate pathology. CHS, contact hypersensitivity; CLP, cecal ligation and puncture; ET-1, endothelin-1; IgE, immunoglobulin E; IL, interleukin; MC, mast cell; NLRP3, nucleotide-binding oligomerization domain–leucine-rich repeats containing pyrin domain 3; NT, neurotensin; TLR, Toll-like receptor; TNF, tumor necrosis factor; UVB, ultraviolet B irradiation; VDR, vitamin D receptor.