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  • Review Article
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Mast cell-orchestrated immunity to pathogens

Nature Reviews Immunology volume 10, pages 440–452 (2010)Cite this article

Subjects

Key Points

  • Although widely associated with various inflammatory diseases, mast cells have an evolutionarily conserved role in host defence and have been shown to make functional contributions to immunity to a broad range of pathogens including bacteria, parasites and possibly viruses.

  • Functioning as sentinels, mast cells quickly recognize pathogens during primary and subsequent infections through various direct and indirect receptors, including Toll-like receptors, receptors for endogenous host by-products of inflammation and Fc receptors, which can bind pathogens through high-affinity antibody-mediated interactions.

  • Mast cells have the potential to be the first responding cell type at a site of infection owing to their ability to degranulate in response to many signs of inflammation and infection and release preformed mediators within seconds of activation.

  • A key function of mast cells during infection is to communicate with many cell types, such as dendritic cells, lymphocytes, neutrophils, macrophages, epithelial cells, endothelial cells and neural cells, both locally at a site of infection and in distant tissues such as lymph nodes.

  • Mast cells act as catalysts for immune responses to pathogens, enhancing the speed and magnitude of both innate and adaptive immune responses, and they can also influence the character of responses by producing unique factors depending on the type of pathogen challenge. These qualities also make them effective targets to enhance immune responses to vaccine antigens.

  • Unique attributes of mast cells, including their abilities to survive after activation, replenish their granules, replicate at sites of inflammation and bind pathogen-specific antibodies after a primary response, highlight their potential to contribute to immunological memory, which may influence host responses to chronic or secondary infections.

Abstract

Although mast cells were discovered more than a century ago, their functions beyond their role in allergic responses remained elusive until recently. However, there is a growing appreciation that an important physiological function of these cells is the recognition of pathogens and modulation of appropriate immune responses. Because of their ability to instantly release several pro-inflammatory mediators from intracellular stores and their location at the host–environment interface, mast cells have been shown to be crucial for optimal immune responses during infection. Mast cells seem to exert these effects by altering the inflammatory environment after detection of a pathogen and by mobilizing various immune cells to the site of infection and to draining lymph nodes. Interestingly, the character and timing of these responses can vary depending on the type of pathogen stimulus, location of pathogen recognition and sensitization state of the responding mast cells. Recent studies using mast cell activators as effective vaccine adjuvants show the potential of harnessing these cells to confer protective immunity against microbial pathogens.

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Figure 1: Mast cells are strategically located in host peripheral tissues.
Figure 2: Cellular communication by mast cells promotes host defence.
Figure 3: Timing of mast cell responses to pathogens.
Figure 4: Cell trafficking responses induced or increased by mast cells.
Figure 5: Pathogen-specific sensitization of mast cells enhances immune responses.

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References

  1. McNeil, H. P., Adachi, R. & Stevens, R. L. Mast cell-restricted tryptases: structure and function in inflammation and pathogen defense. J. Biol. Chem. 282, 20785–20789 (2007).

    Article  CAS  PubMed  Google Scholar 

  2. Woodbury, R. G. et al. Mucosal mast cells are functionally active during spontaneous expulsion of intestinal nematode infections in rat. Nature 312, 450–452 (1984).

    Article  CAS  PubMed  Google Scholar 

  3. Nawa, Y., Kiyota, M., Korenaga, M. & Kotani, M. Defective protective capacity of W/Wv mice against Strongyloides ratti infection and its reconstitution with bone marrow cells. Parasite Immunol. 7, 429–438 (1985). References 2 and 3 are early reports of a functional involvement of mast cells in the expulsion of intestinal parasites.

    Article  CAS  PubMed  Google Scholar 

  4. Abraham, S. N. & Malaviya, R. Mast cells in infection and immunity. Infect. Immun. 65, 3501–3508 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Abe, T., Swieter, M., Imai, T., Hollander, N. D. & Befus, A. D. Mast cell heterogeneity: two-dimensional gel electrophoretic analyses of rat peritoneal and intestinal mucosal mast cells. Eur. J. Immunol. 20, 1941–1947 (1990).

    Article  CAS  PubMed  Google Scholar 

  6. Vliagoftis, H. & Befus, A. D. Rapidly changing perspectives about mast cells at mucosal surfaces. Immunol. Rev. 206, 190–203 (2005).

    Article  CAS  PubMed  Google Scholar 

  7. Metcalfe, D. D., Baram, D. & Mekori, Y. A. Mast cells. Physiol. Rev. 77, 1033–1079 (1997).

    Article  CAS  PubMed  Google Scholar 

  8. Welle, M. Development, significance, and heterogeneity of mast cells with particular regard to the mast cell-specific proteases chymase and tryptase. J. Leukoc. Biol. 61, 233–245 (1997).

    Article  CAS  PubMed  Google Scholar 

  9. Ghildyal, N., McNeil, H. P., Gurish, M. F., Austen, K. F. & Stevens, R. L. Transcriptional regulation of the mucosal mast cell-specific protease gene, MMCP-2, by interleukin 10 and interleukin 3. J. Biol. Chem. 267, 8473–8477 (1992).

    CAS  PubMed  Google Scholar 

  10. Toru, H. et al. Interleukin-4 promotes the development of tryptase and chymase double-positive human mast cells accompanied by cell maturation. Blood 91, 187–195 (1998).

    CAS  PubMed  Google Scholar 

  11. Oskeritzian, C. A. et al. Surface CD88 functionally distinguishes the MCTC from the MCT type of human lung mast cell. J. Allergy Clin. Immunol. 115, 1162–1168 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Burke, S. M. 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 111, 5467–5476 (2008).

    Article  CAS  PubMed  Google Scholar 

  13. Burwen, S. J. Recycling of mast cells following degranulation in vitro: an ultrastructural study. Tissue Cell 14, 125–134 (1982).

    Article  CAS  PubMed  Google Scholar 

  14. Trinchieri, G. & Sher, A. Cooperation of Toll-like receptor signals in innate immune defence. Nature Rev. Immunol. 7, 179–190 (2007).

    Article  CAS  Google Scholar 

  15. Supajatura, V. et al. Differential responses of mast cell Toll-like receptors 2 and 4 in allergy and innate immunity. J. Clin. Invest. 109, 1351–1359 (2002). One of several papers from this group that shows the crucial in vivo role of mast cell-expressed TLRs in mobilizing immune cells following exposure to microbial products.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Varadaradjalou, S. et al. Toll-like receptor 2 (TLR2) and TLR4 differentially activate human mast cells. Eur. J. Immunol. 33, 899–906 (2003).

    Article  CAS  PubMed  Google Scholar 

  17. Malaviya, R., Gao, Z., Thankavel, K., van der Merwe, P. A. & Abraham, S. N. The mast cell tumor necrosis factor α response to FimH-expressing Escherichia coli is mediated by the glycosylphosphatidylinositol-anchored molecule CD48. Proc. Natl Acad. Sci. USA 96, 8110–8115 (1999). This study describes the identification of a unique receptor on mast cells that recognizes bacteria, triggering mast cell exocytosis of granules and uptake of bacteria.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Munoz, S., Hernandez-Pando, R., Abraham, S. N. & Enciso, J. A. Mast cell activation by Mycobacterium tuberculosis: mediator release and role of CD48. J. Immunol. 170, 5590–5596 (2003).

    Article  CAS  PubMed  Google Scholar 

  19. Rocha-de-Souza, C. M., Berent-Maoz, B., Mankuta, D., Moses, A. E. & Levi-Schaffer, F. Human mast cell activation by Staphylococcus aureus: interleukin-8 and tumor necrosis factor α release and the role of Toll-like receptor 2 and CD48 molecules. Infect. Immun. 76, 4489–4497 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kawakami, T. & Galli, S. J. Regulation of mast-cell and basophil function and survival by IgE. Nature Rev. Immunol. 2, 773–786 (2002).

    Article  CAS  Google Scholar 

  21. Woolhiser, M. R., Okayama, Y., Gilfillan, A. M. & Metcalfe, D. D. IgG-dependent activation of human mast cells following up-regulation of FcγRI by IFN-γ. Eur. J. Immunol. 31, 3298–3307 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. Gurish, M. F. et al. IgE enhances parasite clearance and regulates mast cell responses in mice infected with Trichinella spiralis. J. Immunol. 172, 1139–1145 (2004).

    Article  CAS  PubMed  Google Scholar 

  23. Qiao, H., Andrade, M. V., Lisboa, F. A., Morgan, K. & Beaven, M. A. FcɛR1 and Toll-like receptors mediate synergistic signals to markedly augment production of inflammatory cytokines in murine mast cells. Blood 107, 610–618 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Genovese, A. et al. Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E. Infect. Immun. 68, 5517–5524 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Hirai, Y. et al. A new mast cell degranulating peptide “mastoparan” in the venom of Vespula lewisii. Chem. Pharm. Bull. (Tokyo) 27, 1942–1944 (1979).

    Article  CAS  Google Scholar 

  26. Demeure, C. E. et al. Anopheles mosquito bites activate cutaneous mast cells leading to a local inflammatory response and lymph node hyperplasia. J. Immunol. 174, 3932–3940 (2005). This study shows how mosquito bites can trigger dermal mast cell degranulation and how this can affect the recruitment of immune cells to the site of the insect bite and to the draining lymph node. This may be highly relevant to many insect borne diseases.

    Article  CAS  PubMed  Google Scholar 

  27. Johnson, D. & Krenger, W. Interactions of mast cells with the nervous system — recent advances. Neurochem. Res. 17, 939–951 (1992).

    Article  CAS  PubMed  Google Scholar 

  28. Maurer, M. et al. Mast cells promote homeostasis by limiting endothelin-1-induced toxicity. Nature 432, 512–516 (2004).

    Article  CAS  PubMed  Google Scholar 

  29. Nilsson, G. et al. C3a and C5a are chemotaxins for human mast cells and act through distinct receptors via a pertussis toxin-sensitive signal transduction pathway. J. Immunol. 157, 1693–1698 (1996).

    CAS  PubMed  Google Scholar 

  30. Mullaly, S. C. & Kubes, P. Mast cell-expressed complement receptor, not TLR2, is the main detector of zymosan in peritonitis. Eur. J. Immunol. 37, 224–234 (2007).

    Article  CAS  PubMed  Google Scholar 

  31. Ehrlich, P. Nobel Lecture, December 11, 1908 (Elsevier, Amsterdam, 1967).

    Google Scholar 

  32. Kunder, C. A. et al. Mast cell-derived particles deliver peripheral signals to remote lymph nodes. J. Exp. Med. 206, 2455–2467 (2009). This paper reveals a new mechanism of how peripheral mast cells can regulate distal draining lymph nodes after degranulation by long distance communication through lymphatics using particle-packaged cytokines.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Thakurdas, S. M. et al. The mast cell-restricted tryptase mMCP-6 has a critical immunoprotective role in bacterial infections. J. Biol. Chem. 282, 20809–20815 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Huang, C. et al. Induction of a selective and persistent extravasation of neutrophils into the peritoneal cavity by tryptase mouse mast cell protease 6. J. Immunol. 160, 1910–1919 (1998). This paper describes a role for proteases in neutrophil recruitment.

    CAS  PubMed  Google Scholar 

  35. Tani, K. et al. Chymase is a potent chemoattractant for human monocytes and neutrophils. J. Leukoc. Biol. 67, 585–589 (2000).

    Article  CAS  PubMed  Google Scholar 

  36. Shin, K. et al. Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection. J. Immunol. 180, 4885–4891 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Piliponsky, A. M. et al. Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis. Nature Med. 14, 392–398 (2008). This study reveals a protective role for mast cells following sepsis, through decreasing levels of an endogenous peptide, neurotensin.

    Article  CAS  PubMed  Google Scholar 

  38. Kalesnikoff, J. & Galli, S. J. New developments in mast cell biology. Nature Immunol. 9, 1215–1223 (2008).

    Article  CAS  Google Scholar 

  39. Galli, S. J., Nakae, S. & Tsai, M. Mast cells in the development of adaptive immune responses. Nature Immunol. 6, 135–142 (2005).

    Article  CAS  Google Scholar 

  40. Benyon, R. C., Robinson, C. & Church, M. K. Differential release of histamine and eicosanoids from human skin mast cells activated by IgE-dependent and non-immunological stimuli. Br. J. Pharmacol. 97, 898–904 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Boyce, J. A. Mast cells and eicosanoid mediators: a system of reciprocal paracrine and autocrine regulation. Immunol. Rev. 217, 168–185 (2007).

    Article  CAS  PubMed  Google Scholar 

  42. Datta, Y. H. et al. Peptido-leukotrienes are potent agonists of von Willebrand factor secretion and P-selectin surface expression in human umbilical vein endothelial cells. Circulation 92, 3304–3311 (1995).

    Article  CAS  PubMed  Google Scholar 

  43. McIntyre, T. M., Zimmerman, G. A. & Prescott, S. M. Leukotrienes C4 and D4 stimulate human endothelial cells to synthesize platelet-activating factor and bind neutrophils. Proc. Natl Acad. Sci. USA 83, 2204–2208 (1986).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Malaviya, R. & Abraham, S. N. Role of mast cell leukotrienes in neutrophil recruitment and bacterial clearance in infectious peritonitis. J. Leukoc. Biol. 67, 841–846 (2000).

    Article  CAS  PubMed  Google Scholar 

  45. Funk, C. D. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871–1875 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Caron, G. et al. Histamine induces CD86 expression and chemokine production by human immature dendritic cells. J. Immunol. 166, 6000–6006 (2001).

    Article  CAS  PubMed  Google Scholar 

  47. Nakano, N. et al. Involvement of mast cells in IL-12/23 p40 production is essential for survival from polymicrobial infections. Blood 109, 4846–4855 (2007).

    Article  CAS  PubMed  Google Scholar 

  48. Malaviya, R., Ikeda, T., Ross, E. & Abraham, S. N. Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-α. Nature 381, 77–80 (1996). This was one of the first studies to provide evidence that mast cells promote survival during bacterial infections by promoting innate immune cell recruitment. It also identified TNF as a crucial mast cell-derived factor for neutrophil recruitment.

    Article  CAS  PubMed  Google Scholar 

  49. Shelburne, C. P. et al. Mast cells augment adaptive immunity by orchestrating dendritic cell trafficking through infected tissues. Cell Host Microbe 6, 331–342 (2009). This paper shows the key role of mast cells in recruiting DCs to sites of bacterial infection and in the resulting protective immunity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Orinska, Z. et al. TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment. Blood 106, 978–987 (2005). This report shows that mast cells can respond to virus with a chemotactic response characteristic of CD8+ T cell recruitment, suggesting pathogen-specific responses by mast cells.

    Article  CAS  PubMed  Google Scholar 

  51. Ketavarapu, J. M. et al. Mast cells inhibit intramacrophage Francisella tularensis replication via contact and secreted products including IL-4. Proc. Natl Acad. Sci. USA 105, 9313–9318 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Sutherland, R. E., Olsen, J. S., McKinstry, A., Villalta, S. A. & Wolters, P. J. Mast cell IL-6 improves survival from Klebsiella pneumonia and sepsis by enhancing neutrophil killing. J. Immunol. 181, 5598–5605 (2008).

    Article  CAS  PubMed  Google Scholar 

  53. Orinska, Z. et al. IL-15 constrains mast cell-dependent antibacterial defenses by suppressing chymase activities. Nature Med. 13, 927–934 (2007). This study reveals the complex intracellular interplay of various mast cell products in the regulation of mast cell activity during sepsis.

    Article  CAS  PubMed  Google Scholar 

  54. Grimbaldeston, M. A., Nakae, S., Kalesnikoff, J., Tsai, M. & Galli, S. J. Mast cell-derived interleukin 10 limits skin pathology in contact dermatitis and chronic irradiation with ultraviolet B. Nature Immunol. 8, 1095–1104 (2007).

    Article  CAS  Google Scholar 

  55. Palker, T. J., Dong, G. & Leitner, W. W. Mast cells in innate and adaptive immunity to infection. Eur. J. Immunol. 40, 13–18 (2010).

    Article  CAS  PubMed  Google Scholar 

  56. Peranteau, W. H. et al. IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation. J. Invest. Dermatol. 128, 1852–1860 (2008).

    Article  CAS  PubMed  Google Scholar 

  57. Boesiger, J. et al. Mast cells can secrete vascular permeability factor/vascular endothelial cell growth factor and exhibit enhanced release after immunoglobulin E-dependent upregulation of Fcɛ receptor I expression. J. Exp. Med. 188, 1135–1145 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Sendo, T. et al. Involvement of proteinase-activated receptor-2 in mast cell tryptase-induced barrier dysfunction in bovine aortic endothelial cells. Cell Signal 15, 773–781 (2003).

    Article  CAS  PubMed  Google Scholar 

  59. Heltianu, C., Simionescu, M. & Simionescu, N. Histamine receptors of the microvascular endothelium revealed in situ with a histamine-ferritin conjugate: characteristic high-affinity binding sites in venules. J. Cell Biol. 93, 357–364 (1982).

    Article  CAS  PubMed  Google Scholar 

  60. Gordon, J. R. & Galli, S. J. Mast cells as a source of both preformed and immunologically inducible TNF-α/cachectin. Nature 346, 274–276 (1990). A pivotal report showing that mast cells generate and store TNF, suggesting that they have a role in many inflammatory responses, including microbial infections.

    Article  CAS  PubMed  Google Scholar 

  61. Biedermann, T. et al. Mast cells control neutrophil recruitment during T cell-mediated delayed-type hypersensitivity reactions through tumor necrosis factor and macrophage inflammatory protein 2. J. Exp. Med. 192, 1441–1452 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Di Nardo, A., Vitiello, A. & Gallo, R. L. Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide. J. Immunol. 170, 2274–2278 (2003). This study shows for the first time that antimicrobial actions of mast cells could also be attributable to their expression of antimicrobial peptides.

    Article  CAS  PubMed  Google Scholar 

  63. Margulis, A. et al. Mast cell-dependent contraction of human airway smooth muscle cell-containing collagen gels: influence of cytokines, matrix metalloproteases, and serine proteases. J. Immunol. 183, 1739–1750 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Klimpel, G. R. et al. A role for stem cell factor and c-kit in the murine intestinal tract secretory response to cholera toxin. J. Exp. Med. 182, 1931–1942 (1995).

    Article  CAS  PubMed  Google Scholar 

  65. Pothoulakis, C., Castagliuolo, I. & LaMont, J. T. Nerves and intestinal mast cells modulate responses to enterotoxins. News Physiol. Sci. 13, 58–63 (1998).

    CAS  PubMed  Google Scholar 

  66. Bischoff, S. C. Physiological and pathophysiological functions of intestinal mast cells. Semin. Immunopathol. 31, 185–205 (2009).

    Article  CAS  PubMed  Google Scholar 

  67. McLachlan, J. B. et al. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. Nature Immunol. 4, 1199–1205 (2003). This paper indicates that peripheral mast cells, and specifically their product TNF, activate distal draining lymph nodes promoting hypertrophy in response to infection.

    Article  CAS  Google Scholar 

  68. Jawdat, D. M., Rowden, G. & Marshall, J. S. Mast cells have a pivotal role in TNF-independent lymph node hypertrophy and the mobilization of Langerhans cells in response to bacterial peptidoglycan. J. Immunol. 177, 1755–1762 (2006). This is the first demonstration that mast cells can mobilize a subset of DCs to draining lymph nodes in response to bacterial products.

    Article  CAS  PubMed  Google Scholar 

  69. Amaral, M. M. et al. Histamine improves antigen uptake and cross-presentation by dendritic cells. J. Immunol. 179, 3425–3433 (2007).

    Article  CAS  PubMed  Google Scholar 

  70. Mazzoni, A., Siraganian, R. P., Leifer, C. A. & Segal, D. M. Dendritic cell modulation by mast cells controls the Th1/Th2 balance in responding T cells. J. Immunol. 177, 3577–3581 (2006).

    Article  CAS  PubMed  Google Scholar 

  71. Stelekati, E. et al. Mast cell-mediated antigen presentation regulates CD8+ T cell effector functions. Immunity 31, 665–676 (2009).

    Article  CAS  PubMed  Google Scholar 

  72. Knight, P. A., Wright, S. H., Lawrence, C. E., Paterson, Y. Y. & Miller, H. R. Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1. J. Exp. Med. 192, 1849–1856 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Mekori, Y. A. & Metcalfe, D. D. Mast cell-T cell interactions. J. Allergy Clin. Immunol. 104, 517–523 (1999).

    Article  CAS  PubMed  Google Scholar 

  74. Echtenacher, B., Mannel, D. N. & Hultner, L. Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381, 75–77 (1996). This study was one of the first to provide in vivo evidence of the crucial role of mast cells and TNF in promoting survival of the host during bacterial infections.

    Article  CAS  PubMed  Google Scholar 

  75. Wei, O. L., Hilliard, A., Kalman, D. & Sherman, M. Mast cells limit systemic bacterial dissemination but not colitis in response to Citrobacter rodentium. Infect. Immun. 73, 1978–1985 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Ohnmacht, C. & Voehringer, D. Basophils protect against reinfection with hookworms independently of mast cells and memory Th2 cells. J. Immunol. 184, 344–350 (2010).

    Article  CAS  PubMed  Google Scholar 

  77. Maurer, M. et al. Skin mast cells control T cell-dependent host defense in Leishmania major infections. FASEB J. 20, 2460–2467 (2006).

    Article  CAS  PubMed  Google Scholar 

  78. Newlands, G. F., Coulson, P. S. & Wilson, R. A. Stem cell factor dependent hyperplasia of mucosal-type mast cells but not eosinophils in Schistosoma mansoni-infected rats. Parasite Immunol. 17, 595–598 (1995).

    Article  CAS  PubMed  Google Scholar 

  79. Asai, K. et al. Regulation of mast cell survival by IgE. Immunity 14, 791–800 (2001).

    Article  CAS  PubMed  Google Scholar 

  80. Piliponsky, A. M. et al. Mast cell-derived TNF can exacerbate mortality during severe bacterial infections in C57BL/6–KitW-sh/W-sh mice. Am. J. Pathol. 176, 926–938 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Siebenhaar, F. et al. Control of Pseudomonas aeruginosa skin infections in mice is mast cell-dependent. Am. J. Pathol. 170, 1910–1916 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Wershil, B. K., Castagliuolo, I. & Pothoulakis, C. Direct evidence of mast cell involvement in Clostridium difficile toxin A-induced enteritis in mice. Gastroenterology 114, 956–964 (1998).

    Article  CAS  PubMed  Google Scholar 

  83. Sugiyama, K. Histamine release from rat mast cells induced by Sendai virus. Nature 270, 614–615 (1977). One of the early suggestions of a possible role for mast cells in modulating immune responses to viruses.

    Article  CAS  PubMed  Google Scholar 

  84. Patella, V., Florio, G., Petraroli, A. & Marone, G. HIV-1 gp120 induces IL-4 and IL-13 release from human FcɛRI+ cells through interaction with the VH3 region of IgE. J. Immunol. 164, 589–595 (2000).

    Article  CAS  PubMed  Google Scholar 

  85. Kulka, M., Alexopoulou, L., Flavell, R. A. & Metcalfe, D. D. Activation of mast cells by double-stranded RNA: evidence for activation through Toll-like receptor 3. J. Allergy Clin. Immunol. 114, 174–182 (2004).

    Article  CAS  PubMed  Google Scholar 

  86. Castleman, W. L., Sorkness, R. L., Lemanske, R. F. Jr & McAllister, P. K. Viral bronchiolitis during early life induces increased numbers of bronchiolar mast cells and airway hyperresponsiveness. Am. J. Pathol. 137, 821–831 (1990).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Sorden, S. D. & Castleman, W. L. Virus-induced increases in bronchiolar mast cells in Brown Norway rats are associated with both local mast cell proliferation and increases in blood mast cell precursors. Lab. Invest. 73, 197–204 (1995).

    CAS  PubMed  Google Scholar 

  88. Sundstrom, J. B. et al. Human tissue mast cells are an inducible reservoir of persistent HIV infection. Blood 109, 5293–5300 (2007).

    Article  CAS  PubMed  Google Scholar 

  89. Shirato, K. & Taguchi, F. Mast cell degranulation is induced by A549 airway epithelial cell infected with respiratory syncytial virus. Virology 386, 88–93 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Legrand, L. F., Hotta, H., Hotta, S. & Homma, M. Antibody-mediated enhancement of infection by dengue virus of the P815 murine mastocytoma cell line. Biken J. 29, 51–55 (1986).

    CAS  PubMed  Google Scholar 

  91. McLachlan, J. B. et al. Mast cell activators: a new class of highly effective vaccine adjuvants. Nature Med. 14, 536–541 (2008). The first demonstration of small molecular activators of mast cells as highly effective vaccine adjuvants.

    Article  CAS  PubMed  Google Scholar 

  92. McGowen, A. L., Hale, L. P., Shelburne, C. P., Abraham, S. N. & Staats, H. F. The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen. Vaccine 27, 3544–3552 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Dillon, S. B. & MacDonald, T. T. Limit dilution analysis of mast cell precursor frequency in the gut epithelium of normal and Trichinella spiralis infected mice. Parasite Immunol. 8, 503–511 (1986).

    Article  CAS  PubMed  Google Scholar 

  94. Kasugai, T. et al. Infection with Nippostrongylus brasiliensis induces invasion of mast cell precursors from peripheral blood to small intestine. Blood 85, 1334–1340 (1995).

    CAS  PubMed  Google Scholar 

  95. Madden, K. B. et al. Antibodies to IL-3 and IL-4 suppress helminth-induced intestinal mastocytosis. J. Immunol. 147, 1387–1391 (1991).

    CAS  PubMed  Google Scholar 

  96. Lantz, C. S. et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature 392, 90–93 (1998).

    Article  CAS  PubMed  Google Scholar 

  97. Matsuda, H. et al. Necessity of IgE antibodies and mast cells for manifestation of resistance against larval Haemaphysalis longicornis ticks in mice. J. Immunol. 144, 259–262 (1990).

    CAS  PubMed  Google Scholar 

  98. Furuta, T., Kikuchi, T., Iwakura, Y. & Watanabe, N. Protective roles of mast cells and mast cell-derived TNF in murine malaria. J. Immunol. 177, 3294–3302 (2006). This study provides the first in vivo evidence of a protective role for mast cells against a blood-borne parasite.

    Article  CAS  PubMed  Google Scholar 

  99. Malaviya, R., Ikeda, T. & Abraham, S. N. Contribution of mast cells to bacterial clearance and their proliferation during experimental cystitis induced by type 1 fimbriated E. coli. Immunol. Lett. 91, 103–111 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Xu, X. et al. Mast cells protect mice from Mycoplasma pneumonia. Am. J. Respir. Crit. Care Med. 173, 219–225 (2006).

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors' work is supported by the US National Institutes of Health grants R01 AI35678, R01 DK077159, R01 AI50021, R37 DK50814 and R21 AI056101. We thank M. M. Ng and H. Yap of the National University of Singapore for their help in acquiring the image in Fig. 1a and Z. Swan for reviewing the manuscript.

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Authors and Affiliations

  1. Departments of Immunology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Soman N. Abraham & Ashley L. St. John

  2. Pathology and Molecular Genetics and Microbiology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Soman N. Abraham

  3. Program in Emerging Infectious Diseases, DUKE-National University of Singapore Graduate Medical School, Singapore, 169857

    Soman N. Abraham

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  1. Soman N. Abraham
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  2. Ashley L. St. John
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Correspondence to Soman N. Abraham.

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The authors declare no competing financial interests.

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Abraham, S., St. John, A. Mast cell-orchestrated immunity to pathogens. Nat Rev Immunol 10, 440–452 (2010). https://doi.org/10.1038/nri2782

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  • DOI: https://doi.org/10.1038/nri2782

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