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Intracellular TLRs of Mast Cells in Innate and Acquired Immunity

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Toll-like Receptors in Health and Disease

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 276))

Abstract

Mast cells (MCs) distribute to interface tissues with environment, such as skin, airway, and gut mucosa, thereby functioning as the sentinel against invading allergens and pathogens. To respond to and exclude these external substances promptly, MCs possess granules containing inflammatory mediators, including heparin, proteases, tumor necrosis factor, and histamine, and produce these mediators as a consequence of degranulation within minutes of activation. As a delayed response to external substances, MCs de novo synthesize inflammatory mediators, such as cytokines and chemokines, by sensing pathogen- and damage-associated molecular patterns through their pattern recognition receptors, including Toll-like receptors (TLRs). A substantial number of studies have reported immune responses by MCs through surface TLR signaling, particularly TLR2 and TLR4. However, less attention has been paid to immune responses through nucleic acid-recognizing intracellular TLRs. Among intracellular TLRs, human and rodent MCs express TLR3, TLR7, and TLR9, but not TLR8. Some virus infections modulate intracellular TLR expression in MCs. MC-derived mediators, such as histamine, cysteinyl leukotrienes, LL-37, and the granulocyte-macrophage colony-stimulating factor, have also been reported to modulate intracellular TLR expression in an autocrine and/or paracrine fashion. Synthetic ligands for intracellular TLRs and some viruses are sensed by intracellular TLRs of MCs, leading to the production of inflammatory cytokines and chemokines including type I interferons. These MC responses initiate and facilitate innate responses and the subsequent recruitment of additional innate effector cells. MCs also associate with the regulation of adaptive immunity. In this overview, the expression of intracellular TLRs in MCs and the recognition of pathogens, including viruses, by intracellular TLRs in MCs were critically evaluated.

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Acknowledgement

We thank all the colleagues of our department, in particular, the former colleagues who were engaged in MC research: Rui Aoki, Hironori Matsushima, Nobuo Yamada, and Hiroyuki Matsue.

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Authors and Affiliations

  1. Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

    Youichi Ogawa, Manao Kinoshita, Tatsuyoshi Kawamura & Shinji Shimada

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  1. Youichi Ogawa
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  2. Manao Kinoshita
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  3. Tatsuyoshi Kawamura
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  4. Shinji Shimada
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Correspondence to Youichi Ogawa .

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  1. Department of Pediatrics, Division of Allergy and Immunology, Duke University Medical Center (DUMC), Durham, NC, USA

    Vijay Kumar

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Ogawa, Y., Kinoshita, M., Kawamura, T., Shimada, S. (2021). Intracellular TLRs of Mast Cells in Innate and Acquired Immunity. In: Kumar, V. (eds) Toll-like Receptors in Health and Disease. Handbook of Experimental Pharmacology, vol 276. Springer, Cham. https://doi.org/10.1007/164_2021_540

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