The Effect of Bacterial, Viral and Fungal Infection on Mast Cell Reactivity in the Allergic Setting (original) (raw)

The role of human mast cells in allergy and asthma

Bioengineered, 2022

Mast cells are tissue-inhabiting cells that play an important role in inflammatory diseases of the airway tract. Mast cells arise in the bone marrow as progenitor cells and complete their differentiation in tissues exposed to the external environment, such as the skin and respiratory tract, and are among the first to respond to bacterial and parasitic infections. Mast cells express a variety of receptors that enable them to respond to a wide range of stimulants, including the high-affinity FcεRI receptor. Upon initial contact with an antigen, mast cells are sensitized with IgE to recognize the allergen upon further contact. FcεRI-activated mast cells are known to release histamine and proteases that contribute to asthma symptoms. They release a variety of cytokines and lipid mediators that contribute to immune cell accumulation and tissue remodeling in asthma. Mast cell mediators trigger inflammation and also have a protective effect. This review aims to update the existing knowledge on the mediators released by human FcεRI-activated mast cells, and to unravel their pathological and protective roles in asthma and allergy. In addition, we highlight other diseases that arise from mast cell dysfunction, the therapeutic approaches used to address them, and fill the gaps in our current knowledge. Mast cell mediators not only trigger inflammation but may also have a protective effect. Given the differences between human and animal mast cells, this review focuses on the mediators released by human FcεRI-activated mast cells and the role they play in asthma and allergy.

The Critical Role of Mast Cells in Allergy and Inflammation

Annals of the New York Academy of Sciences, 2006

Mast cells are well known for their involvement in allergic and anaphylactic reactions, but recent findings implicate them in a variety of inflammatory diseases affecting different organs, including the heart, joints, lungs, and skin. In these cases, mast cells appear to be activated by triggers other than aggregation of their IgE receptors (FcRI), such as anaphylatoxins, immunoglobulin-free light chains, superantigens, neuropeptides, and cytokines leading to selective release of mediators without degranulation. These findings could explain inflammatory diseases, such as asthma, atopic dermatitis, coronary inflammation, and inflammatory arthritis, all of which worsen by stress. It is proposed that the pathogenesis of these diseases involve mast cell activation by local release of corticotropin-releasing hormone (CRH) or related peptides. Combination of CRH receptor antagonists and mast cell inhibitors may present novel therapeutic interventions.

Allergen and Pathogenic Challenges Initiate Heterogenous Responses in Mast Cells

2017

Mast Cells (MCs) are highly granulated tissue dwelling cells, widely distributed throughout the body in connective tissue and adjacent to mucosal surface where they are frequently located in close proximity to blood vessels and periphery. Due to this strategic location, they are one of the first cells encountering environmental stimuli such as pathogenic microorganisms, allergens and toxins. On their activation, they release large number of pro-inflammatory and immune-regulatory mediators like lysosomal enzymes (β-hexosaminidase, cathapsin-D), vasoactive amines (histamine, serotonin), proteases (tryptase, chymase, carboxypeptidase-A), lipid mediators (leukotrines, prostaglandins), chemokines and cytokines. Our previous studies have shown that these mediators reside in distinct secretory granule subsets whose exocytosis is regulated by different fusion mediator proteins. This led to the hypothesis that the array of mediator release from MCs may also vary in response to different stim...

Mast cells in infection and immunity

Infection and immunity, 1997

Mast cells remain one of the most enigmatic cells in the body. These cells secrete significant amounts of numerous proinflammatory mediators which contribute to a number of chronic inflammatory conditions, including stress-induced intestinal ulceration, rheumatoid arthritis, interstitial cystitis, scleroderma, and Crohn's disease (6, 14, 24, 76). Mast cells are also prominent in the development of anaphylaxis (14, 24, 76). Yet despite the negative effects of their secretions, mast cells or mast cell-like cells have been described even among the lowest order of animals (31). The phylogenic persistence of these cells through evolution strongly suggests that they are beneficial in some fashion to the host. Mast cells are selectively found in relatively large numbers adjacent to blood or lymphatic vessels but are most prominent immediately beneath the epithelial surfaces of the skin and the mucosae of the genitourinary, gastrointestinal, and respiratory tracts. Estimated concentrations of mast cells range from 500 to 4,000 per mm 3 in the lungs, 7,000 to 12,000 per mm 3 in skin, and 20,000 per mm 3 in the gastrointestinal tract (76). Because many of these sites also happen to be portals of infection, mast cells may represent one of the first inflammatory cells encountered by an invading pathogen. There is considerable evidence that mast cells recognize and react to a wide range of microorganisms or their products (Table 1). Such interactions lend further credence to the notion that mast cells have the potential to markedly influence the course of microbial infections. In this paper, we review data that support the possibility that the raison d'être for the mast cell is initiating and coordinating the host's inflammatory and immune responses against microbial pathogens. SPECIFIC MAST CELL RECOGNITION OF MICROBIAL PATHOGENS

Mast cells – key effector cells in immune responses

Trends in Immunology, 2007

Mast cells are best known for their potent effector functions in allergic disorders. In recent years, however, mast cells have been identified to be involved in a surprisingly complex range of immune functions that go far beyond allergies and include the development of autoimmune disorders and peripheral tolerance, and the initiation and maintenance of adaptive and innate host responses. Here, we review the key signals and effector mechanisms that have lately been identified for mast cell functions in these immune responses.

Mast cells as regulators of skin inflammation and immunity

Acta dermato-venereologica, 2011

Mast cells are known to be the effector cells of immediate-type allergy, but experimental evidence obtained during the last decade has revealed their role in innate and acquired immunity. Upon activation mast cells can undergo an anaphylactic or piecemeal degranulation or degranulation-independent mediator secretion, resulting in rapid or slow release of soluble mediators, such as serine proteinases, histamine, lipid-derived mediators, cytokines, chemokines and growth factors. Mast cells can express different receptors and ligands on the cell surface, molecules that can activate the cells of the immune system, such as different subsets of T cells. All these mediators and cell surface molecules can promote inflammation in the skin. During the last years, a new role for mast cells has emerged; induction of tolerance or immunosuppression and interaction with regulatory T cells. However, the mechanisms that switch the proinflammatory function of mast cells to an immunosuppressive one ar...