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Allergic Consequences

Mast cells reside in tissues closely associated with blood vessels or on the surface of the body, particularly in the skin and mucous membranes. Therefore, in addition to their roles as effector cells in IgE-mediated allergic diseases, mast cells are widely regarded as important innate immune cells.1

The roles of mast cells in immune surveillance and innate immunity against bacterial pathogens have been well defined. In general, innate host immune responses to various pathogens are initiated by the recognition of specific microbial components, such as lipopolysaccharides (LPS), lipoproteins, flagellins, and nucleic acids, by pattern recognition receptors (PRRs). The recognition of microbial components by PRRs results in the coordinated activation of transcription factors, leading to the expression of inflammatory cytokines, chemokines and type I interferons (IFNs). They previously demonstrated that mast cells contribute to innate immune responses against invasive bacteria by expressing PRRs, such as TLRs-2,3,4,5,6,6,7 and 9, which respond to specific ligands inducing the production of cytokines and chemokines or the release of granular cell content. Similarly, innate immune responses against viral infection begin with the recognition of the virus by specific PRRs. As described above, viral nucleic acids are recognized by different types of sensors: TLRs, which detect double-stranded RNA (ds) or single-stranded RNA (ss) in the endosome; retinoic acid reproducible I-type genetic receptors (RLR), which recognize viral RNA in the cytoplasm; and DNA sensors, which detect cytoplasmic viral DNA.1 The viral DNA is detected by TLRs, which detect double-stranded RNA (ds) or single-stranded RNA (ss) in the endosome; type I genetic receptors (RLR) reproducible in retinoic acid (RLR), which recognize viral RNA in the cytoplasm; and DNA sensors, which detect cytoplasmic viral DNA1

It has previously been demonstrated that human mast cells express TLR3, a poly (I: C) and dsRNA receptor. The activation of mast cells, including the specific production of antiviral cytokines such as type I interferon or the release of their granular content, has been observed at the time of stimulation with viruses, viral products or poly I: C. In addition, evidence has been accumulating regarding the role of mast cells in response to viral infections. Orinska et al. reported the functional consequences of mast cell activation in response to viral infection. They demonstrated that mast cells stimulated via TLR3 produced chemokines that mediated CD8+ T cell recruitment in vivo.  In addition, TLR-induced activation of mast cells by LPS or poly I: C increased the ability of mast cells to activate CD8+ T cells. More recently, mast cells have been shown to play an important role in protecting the host from infection by herpes simplex virus 2 (HSV-2).1

Burke et al. found that poly I: C-exposed or reovirus-infected mast cells recruit NK cells in a CXCL8-dependent manner. It was demonstrated that mammalian reovirus, an RNA virus that is normally effectively controlled by the immune response, can infect human mast cells and induce the production of large amounts of CXCL8. These CXCL8 responses are sufficient to induce the chemotaxis of NK CD56+ cells, and CXCR1 expressed in NK cells plays an important role in this response. It has been suggested that NK cells express the CXCL8, CXCR1 and CXCR2 receptors, and this study confirmed these data, although there is some controversy in this area. Since CXCL8 is also a potent neutrophil chemoatrayent, the data from this study suggest a possible role of mast cells in the simultaneous recruitment of neutrophils that may contribute to the immune response against viral infection.2

It has also been shown that mast cells recruit many other types of effector cells into inflamed tissues, including blood monocytes and granulocytes (such as eosinophils) during infection or in models of allergic disease.2

Mast cell stimulation through NK cell chemotaxis enhances the recognized ability of mast cells to serve as sentinel cells in the recruitment of effector cells in bacterial infections, nematode parasitic infections, and in the recruitment of NK cells in viral infections.2

It is important to clarify the mechanisms of virus recognition that lead to mast cell activation to understand the role played by mast cells in viral infection, since mast cells function not only as innate immune cells for host protection, but also as exaggerators of allergic diseases associated with viral infection.1

Therefore, current findings reinforce the role of mast cells as key immune response responders during the early stages of viral infection through their ability to directly recognize and respond quickly to a virus through the rapid production of cytokines and antiviral chemokines using RLRs and OAS-RNase L, in addition to TLR3. In particular, both allergens and microbial antigens can trigger mast cell activation, and allergic or autoimmune diseases, where mast cells play an important role in their pathogenesis, which are often exacerbated by viruses such as rhinovirus.1 As shown in our article, EBV also activates TLR3 and can generate this response from mast cells.


  1. Tsutsui-Takeuchi M, Ushio H, Fukuda M, et al. Roles of retinoic acid-inducible gene-I-like receptors (RLRs), Toll-like receptor (TLR) 3 and 2′-5′ oligoadenylate synthetase as viral recognition receptors on human mast cells in response to viral infection.Immunologic Research. 2015;61(3):240-249. Available in:
  2. Sarah M. Burke, Thomas B. Issekutz, Karkada Mohan, et al. Human mast cell activation with virus-associated stimuli leads to the selective chemotaxis of natural killer cells by a CXCL8-dependent mechanism. Blood Jun 2008, 111 (12) 5467-5476. Available in: