Skip to main content

Advertisement

SpringerLink
Log in

Staphylococcus aureus superantigens and airway disease

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

Abstract

Twenty-five percent of the population are permanent carriers of Staphylococcus aureus, possibly producing a variety of toxins with superantigenic properties. Staphylococcal superantigens are a group of highmolecular-weight pyrogenic proteins that have in common an extremely potent stimulatory activity for T-lymphocytes, macrophages, mast cells, eosinophils, and epithelial cells. The role of staphylococcal superantigens in atopic dermatitis has recently been recognized, and new evidence suggests that similar mechanisms may also be relevant in airway disease. This circumstantial evidence is currently limited to rhinitis, sinusitis, and possibly ashtma, but may, if supported, open a new understanding of pathomechanisms and therapeutic targets.

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. Farthing MJH, Jeffries DJ, Anderson J: Infectious diseases, tropical medicine and sexually transmitted diseases. In Clinical Medicine, edn. 3. Edited by Kumar P, Clark M. London: Baillière Tindall; 1994:1–105.

    Google Scholar 

  2. Balaban N, Rasooly A: Staphylococcal enterotoxins. Int J Food Microbiol 2000, 61:1–10.

    Article  PubMed  CAS  Google Scholar 

  3. Yarwood JM, McCormick JK, Schlievert PM: Identification of a novel two-component regulatory system that acts in global regulation of virulence factors of Staphylococcus aureus. J Bacteriol 2001, 183:1113–1123.

    Article  PubMed  CAS  Google Scholar 

  4. Fleischer B: Superantigens. APMIS 1994, 102:3–12.

    Article  PubMed  CAS  Google Scholar 

  5. Wood SC, Holsapple MP: Direct suppression of superantigeninduced IgM secretion in human lymphocytes by 2,3,7,8-TCDD. Toxicol Appl Pharmacol 1993, 122:308–313.

    Article  PubMed  CAS  Google Scholar 

  6. Cullen CM, Blanco LR, Bonventre PE, Choi E: A toxic shock syndrome toxin-1 mutant that defines a functional site critical for T-cell activation. Infect Immun 1995, 63:2141–2146.

    PubMed  CAS  Google Scholar 

  7. Ladhani S, Joannou CL, Lochrie DP, et al.: Clinical, microbial, and biochemical aspects of the exfoliative toxins causing staphylococcal scalded-skin syndrome. Clin Microbiol Rev 1999, 12:224–242.

    PubMed  CAS  Google Scholar 

  8. Monday SR, Vath GM, Ferens WA, et al.: Unique superantigen activity of staphylococcal exfoliative toxins. J Immunol 1999, 162:4550–4559.

    PubMed  CAS  Google Scholar 

  9. Silverman G: Adoptive transfer of a superantigen-induced hole in the repertoire of natural IgM-secreting cells. Cell Immunol 2001, 209:76–80.

    Article  PubMed  CAS  Google Scholar 

  10. Mitchell DT, Levitt DG, Schlievert PM, Ohlendorf DH: Structural evidence for the evolution of pyrogenic toxin superantigens. J Mol Evol 2000, 51:520–531.

    PubMed  CAS  Google Scholar 

  11. Li H, Llera A, Malchiodi EL, Mariuzza RA: The structural basis of T-cell activation by superantigens. Ann Rev Immunol 1999, 17:435–466.

    Article  CAS  Google Scholar 

  12. Mollick JA, McMasters RL, Grossmann D, Rich RR: Localization of a site on bacterial superantigens that determines T-cell receptor beta chain specificity. J Exp Med 1993, 177:283–293.

    Article  PubMed  CAS  Google Scholar 

  13. Haffner AC, Zepter K, Elmets CA: Major histocompatibility complex I molecule serves as a ligand for presentation of the superantigen staphylococcal enterotoxin B to T-cells. Proc Nat Acad Sci 1996, 93:3037–3042.

    Article  PubMed  CAS  Google Scholar 

  14. Breuer K, Kapp A, Werfel T: Bacterial infections and atopic dermatitis. Allergy 2001, 56:1034–1041. This review provides an interesting summary of what is known about the impact of superantigens in atopic dermatitis, and how difficult it may be to get rid of them!

    Article  PubMed  CAS  Google Scholar 

  15. Hong SC, Waterbury G, Janeway CA Jr.: Different superantigens interact with distinct sites in the Vbeta domain of a single T-cell receptor. J Exp Med 1996, 183:1437–1446.

    Article  PubMed  CAS  Google Scholar 

  16. Jappe U: Superantigens and their association with dermatological inflammatory diseases: facts and hypotheses. Acta Derm Venereol 2000, 80:321–328.

    Article  PubMed  CAS  Google Scholar 

  17. Krakauer T: Immune response to staphylococcal superantigens. Immunol Res 1999, 20:163–173.

    PubMed  CAS  Google Scholar 

  18. Aroeira LS, Martinez AC: The role of IL-4 in the staphylococcal enterotoxin B-triggered immune response: increased susceptibility to shock and deletion of CD8Vbeta8+ T-cells in IL-4 knockout mice. Eur J Immunol 1999, 29:1397–1405.

    Article  PubMed  CAS  Google Scholar 

  19. Krakauer T: Cell adhesion molecules are co-receptors for staphylococcal enterotoxin B-induced T-cell activation and cytokine production. Immunol Lett 1994, 39:121–125.

    Article  PubMed  CAS  Google Scholar 

  20. Lamphear JG, Stevens KR, Rich RR: Intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 provide co-stimulation for superantigen-induced T-lymphocyte proliferation in the absence of a specific presenting molecule. J Immunol 1998, 160:615–623.

    PubMed  CAS  Google Scholar 

  21. Joss A, Akdis M, Faith A, et al.: IL-10 directly acts on T-cells by specifically altering the CD28 co-stimulation pathway. Eur J Immunol 2000, 30:1683–1690.

    Article  PubMed  CAS  Google Scholar 

  22. Das T, Sa G, Ray PK: Mechanisms of protein A superantigeninduced signal transduction for proliferation of mouse B-cell. Immunol Lett 1999, 70:45–51.

    Article  Google Scholar 

  23. Domiati-Saad R, Attrep JF, Brezinschek HP, et al.: Staphylococcal enterotoxin D functions as a human B-cell superantigen by rescuing VH4-expressing B-cells from apoptosis. J Immunol 1996, 156:3608–3620.

    PubMed  CAS  Google Scholar 

  24. Jabara HH, Geha RS: The superantigen toxic shock syndrome toxin-1 induces CD40 ligand expression and modulates IgE isotype switching. Int Immunol 1996, 8:1503–1510.

    Article  PubMed  CAS  Google Scholar 

  25. Hofer ME, Lester MR, Schlievert PM, Leung DY: Upregulation of IgE synthesis by staphylococcal toxic shock syndrome toxin-1 in peripheral blood mononuclear cells from patients with atopic dermatitis. Clin Exp Allergy 1995, 25:1218–1227.

    Article  PubMed  CAS  Google Scholar 

  26. Tumang JR, Zhou JL, Gietl D, et al.: T-helper cell dependent microbial superantigen-mediated B-cell activation in vivo. Autoimmunity 1996, 24:247–255.

    PubMed  CAS  Google Scholar 

  27. Hofer ME, Harbeck RJ, Schlievert PM, Leung DY: Staphylococcal toxins augment specific IgE responses by atopic patients exposed to allergen. J Invest Dermatol 1999, 112:171–176.

    Article  PubMed  CAS  Google Scholar 

  28. Mawhorter SD, Kazura JW, Boom WH: Human eosinophils as antigen-presenting cells: relative efficiency for superantigen- and antigen-induced CD4+ T-cell proliferation. Immunol 1994, 81:584–591.

    CAS  Google Scholar 

  29. Wedi B, Wieczorek D, Stünkel T, Kapp A: Pro-inflammatory effects of staphylococcal exotoxins on eosinophils: Inhibition of apoptosis and modulation of cell surface antigens [abstract]. Allergy 2001, 56(Suppl 68):121–122.

    Google Scholar 

  30. Miller EJ, Nagao S, Carr FK, et al.: Interleukin-8 (IL-8) is a major neutrophil chemotaxin from human alveolar macrophages stimulated with staphylococcal enterotoxin A (SEA). Inflamm Res 1996, 45:386–392.

    Article  PubMed  CAS  Google Scholar 

  31. Wright AD, Chapes SK: Cross-linking staphylococcal enterotoxin A bound to major histocompatibility complex class I is required for TNF-alpha secretion. Cell Immunol 1999, 197:129–135.

    Article  PubMed  CAS  Google Scholar 

  32. Bright JJ, Xin Z, Sriram S: Superantigens augment antigenspecific Th1 responses by inducing IL-12 production in macrophages. J Leukoc Biol 1999, 65:665–670.

    PubMed  CAS  Google Scholar 

  33. Genovese A, Bouvet JP, Florio G, et al.: Bacterial immunoglobulin superantigen proteins A and L activate human heart mast cells by interacting with immunoglobulin E. Infect Immun 2000, 68:5517–5524.

    Article  PubMed  CAS  Google Scholar 

  34. Ackermann L, Pelkonen J, Harvima IT: Staphylococcal enterotoxin B inhibits the production of interleukin-4 in a human mast-cell line HMC-1. Immunol 1998, 94:247–252.

    Article  CAS  Google Scholar 

  35. Thakur A, Clegg A, Chauhan A, Willcox MD: Modulation of cytokine production from an epiocular corneal cell culture model in response to Staphylococcus aureus superantigen. Aust N Z J Opthalmol 1997, 25(Suppl 1):S43-S45.

    Google Scholar 

  36. McKay DM, Lu J, Jedrkiewixz S, et al.: Nitric oxide participates in the recovery of normal jejunal epithelial ion transport following exposure to the superantigen, Staphylococcus aureus enterotoxin. Br J Immunol 1999, 163:4519–4526.

    CAS  Google Scholar 

  37. McKay DM, Singh PK: Superantigen activation of immune cells evokes epithelial (T84) transport and barrier abnormalities via IFN-gamma and TNF alpha: inhibition of increased permeability but not diminished secretory responses by TGF-beta2. J Immunol 1997, 159:2382–2390.

    PubMed  CAS  Google Scholar 

  38. Bacigaluppi JE, Negroni R, de Severino HM: Bacterial allergy in allergic rhinitis and bronchial asthma. Ann Allergy 1979, 42:95–98.

    PubMed  CAS  Google Scholar 

  39. Bachert C, Gevaert P, Holtappels G, et al.: Total and specific IgE in nasal polyps is related to local eosinophilic inflammation. J Allergy Clin Immunol 2001, 107:607–614. This paper is the first report on the possible role of Staphylococcus aureus superantigens A and B in human airways. Of interest is the relation to the severity of local eosinophilic disease, and to asthma and aspirin sensitivity. These findings will lead to further investigations in lower airway disease.

    Article  PubMed  CAS  Google Scholar 

  40. Clementsen P, Jensen CB, Jarlov JO, et al.: Influenza A virus enhances Stapyhlococcus aureus-induced basophil histamine release in normal individuals and patients with intrinsic asthma. Allergy 1989, 44:39–44.

    Article  PubMed  CAS  Google Scholar 

  41. Clementsen P, Norn S, Kristensen KS, et al.: Bacteria and endotoxin enhance basophil histamine release and potentiation is abolished by carbohydrates. Allergy 1990, 45:402–408.

    Article  PubMed  CAS  Google Scholar 

  42. Oehling A, Aguila de la Coba R, Fernandez M, et al.: Potentiation of histamine release against inhalant allergens (Dermatophagoides pteronyssinus) with bacterial antigens in bronchial asthma. J Invest Allergol Clin Immunol 1997, 7:211–216.

    CAS  Google Scholar 

  43. Hauk PJ, Wenzel SE, Trumble AE, et al.: Increased T-cell receptor vbeta8+ T cells in bronchoalveolar lavage fluid of subjects with poorly controlled asthma: a potential role for microbial superantigens. J Allergy Clin Immunol 1999, 104:37–45. The first indirect evidence for a possible role of SAEs in the subgroup of severe, poorly controlled asthmatics.

    Article  PubMed  CAS  Google Scholar 

  44. Hauk PJ, Hamid QA, Chrousos GP, Leung DY: Induction of corticosteroid insensitivity in human PBMCs by microbial superantigens. J Allergy Clin Immunol 2000, 105:782–787. The in vitro-findings described here point to a possible role of SAEs in severe forms of inflammation as inducers of steroid insensitivity, which could induce poor disease control in nasal or bronchial eosinophilic disease such as nasal polyposis or severe asthma.

    Article  PubMed  CAS  Google Scholar 

  45. Ben-Ari J, Gozal D, Dorio RJ, et al.: Superantigens and cystic fibrosis: resistance of presenting cells to dexamethasone. Clin Diagn Lab Immunol 2000, 7:553–556.

    Article  PubMed  CAS  Google Scholar 

  46. Herz U, Ruckert R, Wollenhaupt K, et al.: Airway exposure to bacterial superantigen (SEB) induces lymphocyte-dependent airway inflammation associated with increased airway responsiveness—a model for non-allergic asthma. Eur J Immunol 1999, 29:1021–1021. Although the question of the relevance of animal findings for humans always remains, these studies in animals have shown that SEB triggers airway recruitment of several pro-inflammatory cell types and release of cytokines, which are associated with increased airway responsiveness in this animal model.

    Article  PubMed  CAS  Google Scholar 

  47. Herz U, Braun A, Ruckert R, Renz H: Various immunological phenotypes are associated with increased airway responsiveness. Clin Exp Allergy 1998, 28:625–634.

    Article  PubMed  CAS  Google Scholar 

  48. Vandenbussche T, De Moor S, Bachert C, van Cauwenberge P: Value of antral puncture in the intensive care patient with fever of unknown origin. Laryngoscope 2000, 110:1702–1706.

    Article  PubMed  CAS  Google Scholar 

  49. Gordts F, Halewyck S, Pierard D, et al.: Microbiology of the middle meatus: a comparison between normal adults and children. J Laryngol Otol 2000, 114:184–188.

    Article  PubMed  CAS  Google Scholar 

  50. Shiomori T, Yoshida S, Miyamoto H, Makishima K: Relationship of nasal carriage of Staphylococcus aureus to pathogenesis of perennial allergic rhinitis. J Allergy Clin Immunol 2000, 105:449–454. The rates of nasal carriage of total and superantigen-producing S. aureus were found to be significantly higher in patients with perennial allergic rhinitis, compared with nonallergic control subjects. Moreover, nasal symptom scores were significantly higher in S. aureuspositive compared with S. aureus-negative patients. It is tempting to speculate that some of these patients may develop nasal polyps and asthma over time.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oto-Rhino-Laryngology, Ghent University Hospital, De Pintelaan 185, B-9000, Ghent, Belgium

    Claus Bachert MD, PhD

Authors
  1. Claus Bachert MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Philippe Gevaert MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul van Cauwenberge MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bachert, C., Gevaert, P. & Cauwenberge, P.v. Staphylococcus aureus superantigens and airway disease. Curr Allergy Asthma Rep 2, 252–258 (2002). https://doi.org/10.1007/s11882-002-0027-9

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-002-0027-9

Keywords

Search

Navigation