Skip to main content

Advertisement

SpringerLink
Log in

The role of defensins in virus-induced asthma

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Respiratory viruses appear to play a central role in asthma pathogenesis. In addition to a major role in triggering asthma exacerbations, viral infections early in life may play a role in disease development. Although defensins were initially identi.ed as antimicrobial peptides, recent studies have demonstrated that they have a much broader range of actions that are of relevance to virally induced asthma. Defensins are not only induced during viral infections, they exert direct antiviral actions against some enveloped viruses, and also can impair viral infection of cells. In addition, defensins modulate the activity of several cell types that contribute to innate immunity, including mast cells, epithelial cells, natural killer cells, and dendritic cells. They also have the capacity to modulate adaptive immunity and to contribute to airway remodeling. In this article, recent advances in these areas are reviewed in the context of the potential role of defensins in virus-induced asthma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Gern JE: Viral respiratory infection and the link to asthma. Pediatr Infect Dis J 2004, 23:S78-S86. A balanced and excellent discussion of the role of viruses in the induction and exacerbation of asthma. Links between allergy and the immune system are discussed.

    Article  PubMed  Google Scholar 

  2. Schneider JJ, Unholzer A, Schaller M, et al.: Human defensins. J Mol Med 2005, 83:587–595.

    Article  PubMed  CAS  Google Scholar 

  3. Cole AM, Hong T, Boo LM, et al.: Retrocyclin: a primate peptide that protects cells from infection by T- and M-tropic strains of HIV-1. Proc Natl Acad Sci (USA) 2002, 99:1813–1818.

    Article  CAS  Google Scholar 

  4. Schutte BC, McCray PBJ: Beta-defensins in lung host defense. Annu Rev Physiol 2002, 64:709–748.

    Article  PubMed  CAS  Google Scholar 

  5. Jia HP, Schutte BC, Schudy A, et al.: Discovery of new human beta-defensins using a genomics-based approach. Gene 2001, 263:211–218.

    Article  PubMed  CAS  Google Scholar 

  6. Ganz T, Weiss J: Antimicrobial peptides of phagocytes and epithelia. Semin Hematol 1997, 34:343–354.

    PubMed  CAS  Google Scholar 

  7. Garcia J-RC, Krause A, Schulz S, et al.: Human betadefensin 4: a novel inducible peptide with a speci.c salt-sensitive spectrum of antimicrobial activity. FASEB J 2001, 15:1819–1821.

    PubMed  CAS  Google Scholar 

  8. Ober C, Tsalenko A, Parry R, Cox NJ: A second-generation genomewide screen for asthma-susceptibility alleles in a founder population. Am J Hum Genet 2000, 67:1154–1162.

    PubMed  CAS  Google Scholar 

  9. Hsu FC, Liang KY, Beaty TH: Multipoint linkage disequilibrium mapping approach: incorporating evidence of linkage and linkage disequilibrium from unlinked region. Genet Epidemiol 2003, 25:1–13.

    Article  PubMed  Google Scholar 

  10. Levy H, Raby BA, Lake S, et al.: Association of defensin beta-1 gene polymorphisms with asthma. J Allergy Clin Immunol 2005, 115:252–258. This paper provides the first direct evidence of linkage between polymorphisms in a defensin gene and asthma.

    Article  PubMed  CAS  Google Scholar 

  11. Sahl H-G, Pag U, Bonness S, et al.: Mammalian defensins: structures and mechanism of antibiotic activity. J Leukoc Biol 2005, 77:466–475. An excellent review that provides important insights into the mechanisms of the antimicrobial effects of defensins.

    Article  PubMed  CAS  Google Scholar 

  12. Bals R, Hiemstra PS: Innate immunity in the lung; how epithelial cells fight against respiratory pathogens. Eur Respir J 2004, 23:327–333.

    Article  PubMed  CAS  Google Scholar 

  13. Aarbiou J, Rabe KF, Hiemstra PS: Role of defensins in inflammatory lung disease. Ann Med 2002, 34:96–101.

    Article  PubMed  CAS  Google Scholar 

  14. Yang D, Biragyn A, Hoover DM, et al.: Multiple roles of antimicrobial defensins, cathelicidins, and eosinophilderived neurotoxin in host defense. Annu Rev Immunol 2004, 22:181–215. A comprehensive review of the multiple actions of defensins and other related antimicrobial peptides.

    Article  PubMed  CAS  Google Scholar 

  15. Selsted ME, Ouellette AJ: Mammalian defensins in the antimicrobial immune response. Nat Immunol 2005, 6:551–557.

    Article  PubMed  CAS  Google Scholar 

  16. Kao C-Y, Chen Y, Thai P, et al.: IL-17 markedly upregulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kB signaling pathways. J Immunol 2004, 173:3482–3491.

    PubMed  CAS  Google Scholar 

  17. Molet S, Hamid Q, Davoine F, et al.: IL-17 is increased in asthmatic airways and induces human bronchial fibroblasts to produce cytokines. J Allergy Clin Immunol 2001, 108:430–438.

    Article  PubMed  CAS  Google Scholar 

  18. Hellings PW, Kasran A, Liu Z, et al.: Interleukin-17 orchestrates the granulocyte in.ux into airways after allergen inhalation in a mouse model of allergic asthma. Am J Respir Cell Mol Biol 2003, 28:42–50.

    Article  PubMed  CAS  Google Scholar 

  19. Lindén A, Laan M, Anderson GP: Neutrophils, interleukin-17A and lung disease. Eur Respir J 2005, 25:159–172.

    Article  PubMed  CAS  Google Scholar 

  20. Proud D, Sanders SP, Wiehler S: Human rhinovirus infection induces airway epithelial cell production of human beta-defensin-2 both in vitro and in vivo. J Immunol 2004, 172:4637–4645. This paper provides the first demonstration of human betadefensin production during rhinovirus infections in vitro and in vivo, demonstrates a lack of direct antiviral activity of HBD-2, and provides evidence for a mechanistic link between innate and speci.c immunity.

    PubMed  CAS  Google Scholar 

  21. Duits LA, Nibbering PH, van Strijen E, et al.: Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured human bronchial epithelial cells. FEMS Immunol Med Microbiol 2003, 38:59–64.

    Article  PubMed  CAS  Google Scholar 

  22. Pizzichini MMM, Pizzichini E, Efthimiadis A, et al.: Asthma and natural colds. Inflammatory indices in induced sputum: a feasibility study. Am J Respir Crit Care Med 1998, 158:1178–1184.

    PubMed  CAS  Google Scholar 

  23. Jarjour NN, Gern JE, Kelly EAB, et al.: The effect of an experimental rhinovirus 16 infection on bronchial lavage neutrophils. J Allergy Clin Immunol 2000, 105:1169–1177.

    Article  PubMed  CAS  Google Scholar 

  24. Wark PAB, Johnston SL, Moric I, et al.: Neutrophil degranulation and cell lysis is associated with clinical severity in virus-induced asthma. Eur Respir J 2002, 19:68–75.

    Article  PubMed  CAS  Google Scholar 

  25. Daher KA, Selsted ME, Lehrer RI: Direct inactivation of viruses by human granulocyte defensins. J Virol 1986, 60:1068–1070.

    PubMed  CAS  Google Scholar 

  26. Zhang L, Yu W, He T, et al.: Contribution of human a-defensin 1, 2, and 3 to the anti-HIV activity of CD8 antiviral factor. Science 2002, 298:995–1000.

    Article  PubMed  CAS  Google Scholar 

  27. Chang TL, Vargas JJ, DelPortillo AK, et al.: Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity. J Clin Invest 2005, 115:765–773.

    Article  PubMed  CAS  Google Scholar 

  28. Gropp R, Frye M, Wagner TOF, Bargon J: Epithelial defensins impair adenoviral infection: implication for adenovirus-mediated gene therapy. Hum Gene Ther 1999, 10:957–964.

    Article  PubMed  CAS  Google Scholar 

  29. Leikina E, Delanoe-Ayari H, Melikov K, et al.: Carbohydrate-binding molecules inhibit viral fusion and entry by crosslinking membrane glycoproteins. Nature Immunol 2005, 6:995–1001. An interesting paper that provides important insight into mechanisms by which defensins may limit viral infectivity.

    Article  CAS  Google Scholar 

  30. Niyonsaba F, Iwabuchi K, Matsuda H, et al.: Epithelial cell-derived human beta-defensin-2 acts as a chemotaxin for mast cells through pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol 2002, 14:421–426.

    Article  PubMed  CAS  Google Scholar 

  31. Garcia JR, Jaumann F, Schulz S, et al.: Identi.cation of a novel, multifunctional beta-defensin (human betadefensin-3) with speci.c antimicrobial activity: its interaction with plasma membranes of Xenopus oocytes and the induction of macrophage chemoattraction. Cell Tissue Res 2001, 306:257–264.

    Article  PubMed  CAS  Google Scholar 

  32. Sakamoto N, Mukae H, Fujii T, et al.: Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells. Am J Physiol Lung Cell Mol Physiol 2005, 288:L508-L513.

    Article  PubMed  CAS  Google Scholar 

  33. van Wetering S, Tjabringa GS, Hiemstra PS: Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells. J Leukoc Biol 2005, 77:444–450. An excellent, balanced review of the range of effects of neutrophil defensins on airway epithelial function.

    Article  PubMed  CAS  Google Scholar 

  34. Chaly YV, Paleolog EM, Kolesnikova TS, et al.: Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw 2000, 11:257–266.

    PubMed  CAS  Google Scholar 

  35. McWilliam AS, Napoli S, Marsh AM, et al.: Dendritic cells are recruited into the airway epithelium during the inflammatory response to a broad spectrum of stimuli. J Exp Med 1996, 184:2429–2432.

    Article  PubMed  CAS  Google Scholar 

  36. Yang D, Chen Q, Chertov O, Oppenheim JJ: Human neutrophil defensins selectively chemoattract naive T and immatue dendritic cells. J Leukoc Biol 2000, 68:9–14.

    PubMed  CAS  Google Scholar 

  37. Biragyn A, Ruf.ni PA, Leifer CA, et al.: Toll-like receptor 4-dependent activation of dendritic cells by beta-defensin 2. Science 2002, 298:1025–1029.

    Article  PubMed  CAS  Google Scholar 

  38. Schlender J, Hornung V, Finke S, et al.: Inhibition of Tolllike receptor 7- and 9-mediated alpha/beta interferon production in human plasmacytoid dendritic cells by respiratory syncytial virus and measles virus. J Virol 2005, 79:5507–5515.

    Article  PubMed  CAS  Google Scholar 

  39. Kirchberger S, Majdic O, Steinberger P, et al.: Human rhinoviruses inhibit the accessory function of dendritic cells by inducing sialoadhesin and B7-H1 expression. J Immunol 2005, 175:1145–1152.

    PubMed  CAS  Google Scholar 

  40. Brogden KA, Heidari M, Sacco RE, et al.: Defensin-induced adaptive immunity in mice and its potential in preventing periodontal disease. Oral Microbiol Immunol 2003, 18:95–99.

    Article  PubMed  CAS  Google Scholar 

  41. Biragyn A, Belyakov IM, Chow Y-H, et al.: DNA vaccines encoding human immunode.ciency virus-1 glycoprotein 120 fusions with proinflammatory chemoattractants induce systemic and mucosal immune responses. Blood 2002, 100:1153–1159.

    Article  PubMed  CAS  Google Scholar 

  42. Biragyn A, Surenhu M, Yang D, et al.: Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with nonimmunogenic tumor antigens. J Immunol 2001, 167:6644–6653.

    PubMed  CAS  Google Scholar 

  43. Zhang K, Lu Q, Zhang Q, Hu X: Regulation of activities of NK cells and CD4 expression in T cells by human HNP-1, -2, and -3. Biochem Biophys Res Commun 2004, 323:437–444.

    Article  PubMed  CAS  Google Scholar 

  44. Holgate ST, Davies DE, Lackie PM, et al.: Epithelial-mesenchymal interactions in the pathogenesis of asthma. J Allergy Clin Immunol 2000, 105:193–204.

    Article  PubMed  CAS  Google Scholar 

  45. Aarbiou J, Ertmann M, van Wetering S, et al.: Human neutrophil defensins induce lung epithelial cell proliferation in vitro. J Leukoc Biol 2002, 72:167–174.

    PubMed  CAS  Google Scholar 

  46. McDermott AM, Redfern RL, Zhang B: Human beta-defensin 2 is up-regulated during re-epithelialization of the cornea. Curr Eye Res 2001, 22:64–67.

    Article  PubMed  CAS  Google Scholar 

  47. Aarbiou J, Verhoosel RM, van Wetering S, et al.: Neutrophil defensins enhance lung epithelial wound closure and mucin gene expression in vitro. Am J Respir Cell Mol Biol 2004, 30:193–201. This paper provides strong evidence for a role of neutrophil defensins in wound healing and provides important mechanistic insights into the actions of defensins in this regard.

    Article  PubMed  CAS  Google Scholar 

  48. van Wetering S, van der Linden AC, van Sterkenburg MA, et al.: Regulation of SLPI and ela.n release from bronchial epithelial cells by neutrophil defensins. Am J Physiol Lung Cell Mol Physiol 2000, 278:L51-L58.

    PubMed  Google Scholar 

  49. Ashcroft GS, Lei K, Jin W, et al.: Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med 2000, 6:1147–1153.

    Article  PubMed  CAS  Google Scholar 

  50. Varoga D, Pufe T, Harder J, et al.: Human beta-defensin 3 mediates tissue remodeling processes in articular cartilage by increasing levels of metalloproteinases and reducing levels of their endogenous inhibitors. Arthritis Rheum 2005, 52:1736–1745. This paper provides the first evidence of the ability of defensins to modulate protease antiprotease balance. This could have broad implications if the observations can be extended to the airways.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology and Biophysics, HSC 1627, University of Calgary, 3330 Hospital Drive NW, T2N 4N1, Calgary, Alberta, Canada

    David Proud PhD

Authors
  1. David Proud PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David Proud PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Proud, D. The role of defensins in virus-induced asthma. Curr Allergy Asthma Rep 6, 81–85 (2006). https://doi.org/10.1007/s11882-006-0015-6

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-006-0015-6

Keywords

Search

Navigation