Mast Cell Responses to Viruses and Pathogen Products

Abstract

Mast cells are well accepted as important sentinel cells for host defence against selected pathogens. Their location at mucosal surfaces and ability to mobilize multiple aspects of early immune responses makes them critical contributors to effective immunity in several experimental settings. However, the interactions of mast cells with viruses and pathogen products are complex and can have both detrimental and positive impacts. There is substantial evidence for mast cell mobilization and activation of effector cells and mobilization of dendritic cells following viral challenge. These cells are a major and under-appreciated local source of type I and III interferons following viral challenge. However, mast cells have also been implicated in inappropriate inflammatory responses, long term fibrosis, and vascular leakage associated with viral infections. Progress in combating infection and boosting effective immunity requires a better understanding of mast cell responses to viral infection and the pathogen products and receptors we can employ to modify such responses. In this review, we outline some of the key known responses of mast cells to viral infection and their major responses to pathogen products. We have placed an emphasis on data obtained from human mast cells and aim to provide a framework for considering the complex interactions between mast cells and pathogens with a view to exploiting this knowledge therapeutically. Long-lived resident mast cells and their responses to viruses and pathogen products provide excellent opportunities to modify local immune responses that remain to be fully exploited in cancer immunotherapy, vaccination, and treatment of infectious diseases.

The Effect of Famotidine on SARS-CoV-2 Proteases and Virus Replication

“…Histamine, the H2R ligand, also regulates bronchoconstriction, airway inflammation, and vasodilation 34 . Mast cells are a major source of histamine and their activation has been reported following viral infections of the respiratory tract [35][36][37] . Therefore, Mast cells may represent an underappreciated source of pro-inflammatory cytokine release in COVID-19 patients 35 .…”

Mast Cells: Fascinating but Still Elusive after 140 Years from Their Discovery

“…For several decades mast cells were considered to play mainly proinflammatory roles in several allergic disorders, such as bronchial asthma [2][3][4]122], allergic rhinitis [5], urticaria [6,7], food allergy [8,9], anaphylaxis [10,11], atopic dermatitis [12], and angioedema [13]. During the last years, it became evident that mast cells represent an important cell during bacterial [26,27,29], fungal [29], viral [25,29], and helminth infections [30,31]. Elegant studies have demonstrated that mast cell-derived mediators can play protective roles against several venoms [114,115].…”

“…During the last decades, it was demonstrated that mast cells can also produce different proangiogenic [16][17][18] and lymphangiogenic factors [19,20], suggesting that they may actually play a role in tumor initiation and growth [21][22][23][24]. Moreover, these cells can be activated by different viral [25,26] and bacterial proteins [27,28] and thereby represent a potentially important cell during microbial infections. Therefore, the spectrum of diseases in which mast cells and their mediators have been implicated has extended to include bacterial, fungal, viral, and helminth infections [26,[29][30][31]; several diseases of the cardiovascular [14,32,33] and gastrointestinal systems [34][35][36]; and the joints [37,38].…”

“…Moreover, these cells can be activated by different viral [25,26] and bacterial proteins [27,28] and thereby represent a potentially important cell during microbial infections. Therefore, the spectrum of diseases in which mast cells and their mediators have been implicated has extended to include bacterial, fungal, viral, and helminth infections [26,[29][30][31]; several diseases of the cardiovascular [14,32,33] and gastrointestinal systems [34][35][36]; and the joints [37,38]. Figure 1 schematically summarizes the wide spectrum of pathophysiological conditions in which mast cells and their mediators have been implicated during the last decades.…”

“…This process is facilitated by the mast cell production of TNF-α [80][81][82][83][84] and IL-1β [85,86] that activate endothelial cells, the release of vasoactive mediators (i.e., histamine and cysteinyl leukotrienes) [87,88], and chemokines that promote the recruitment of inflammatory and immune cells [24,70,[89][90][91][92]. Marshall and coworkers elegantly reviewed the complex roles of mast cell responses to viruses and pathogen products [26]. This review highlights the complexity of mast cell biology in the context of innate immune responses.…”