1887

Abstract

Inhalation of conidia is the main cause of invasive pulmonary aspergillosis (IPA) and the respiratory epithelium is the first line of defence. To explore the triggering factor for the inflammatory response to , the species mainly responsible for IPA, this study analysed the differential expression of three inflammatory genes in A549 cells after challenge with live and killed conidia. The influence of steroids, one of the main risk factors for developing IPA, was also investigated. Quantification of mRNAs of the inflammatory mediator genes encoding interleukin (IL)-8, tumour necrosis factor (TNF)- and granulocyte–monocyte colony-stimulating factor (GM-CSF) was carried out using real-time PCR. Ingestion rates were studied for the conidia of and using a fluorescence brightener. Similar results were obtained for both species, with ingestion rates ranging from 35 to 40 %. Exposure of A549 cells to live conidia only induced a four- to fivefold increase in the mRNA levels of the three genes, starting 8 h after the initial contact. Both inactivation of live conidia and treatment by dexamethasone (10 M) prevented the overexpression of TNF-, IL-8 and GM-CSF. Fungal growth, rather than conidia ingestion, appears to be the main stimulus for the production of inflammatory mediators by epithelial cells, and this production is inhibited by steroid therapy. These results underline the role that the epithelium plays in the innate response against IPA.

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2009-02-01
2024-03-29
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References

  1. Asselah T., Bieche I., Laurendeau I., Paradis V., Vidaud D., Degott C., Martinot M., Bedossa P., Valla D. other authors 2005; Liver gene expression signature of mild fibrosis in patients with chronic hepatitis C. Gastroenterology 129:2064–2075 [CrossRef]
    [Google Scholar]
  2. Bieche I., Asselah T., Laurendeau I., Vidaud D., Degot C., Paradis V., Bedossa P., Valla D. C., Marcellin P., Vidaud M. 2005; Molecular profiling of early stage liver fibrosis in patients with chronic hepatitis C virus infection. Virology 332:130–144 [CrossRef]
    [Google Scholar]
  3. Borger P., Koeter G. H., Timmerman J. A., Vellenga E., Tomee J. F., Kauffman H. F. 1999; Proteases from Aspergillus fumigatus induce interleukin (IL)-6 and IL-8 production in airway epithelial cell lines by transcriptional mechanisms. J Infect Dis 180:1267–1274 [CrossRef]
    [Google Scholar]
  4. Botterel F., Gross K., Ibrahim-Granet O., Khoufache K., Escabasse V., Coste A., Cordonnier C., Escudier E., Bretagne S. 2008; Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro. BMC Microbiol 8:97 [CrossRef]
    [Google Scholar]
  5. Chiang L. Y., Sheppard D. C., Gravelat F. N., Patterson T. F., Filler S. G. 2008; Aspergillus fumigatus stimulates leukocyte adhesion molecules and cytokine production by endothelial cells in vitro and during invasive pulmonary disease. Infect Immun 76:3429–3438 [CrossRef]
    [Google Scholar]
  6. Cortez K. J., Lyman C. A., Kottilil S., Kim H. S., Roilides E., Yang J., Fullmer B., Lempicki R., Walsh T. J. 2006; Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus . Infect Immun 74:2353–2365 [CrossRef]
    [Google Scholar]
  7. de Hoog G. S., Guarra J., Gené J., Figueras M. J. 2000 Atlas of Clinical Fungi , 2nd edn. Utrecht, The Netherlands: Centraalbureau voor Schimmelcultures/Reus; Spain: Universitat Rovira i Virgili;
    [Google Scholar]
  8. Hohl T. M., van Epps H. L., Rivera A., Morgan L. A., Chen P. L., Feldmesser M., Pamer E. G. 2005; Aspergillus fumigatus triggers inflammatory responses by stage-specific β -glucan display. PLoS Pathog 1:e30 [CrossRef]
    [Google Scholar]
  9. Huttunen K., Hyvarinen A., Nevalainen A., Komulainen H., Hirvonen M. R. 2003; Production of proinflammatory mediators by indoor air bacteria and fungal spores in mouse and human cell lines. Environ Health Perspect 111:85–92
    [Google Scholar]
  10. Kauffman H. F., Tomee J. F., van de Riet M. A., Timmerman A. J., Borger P. 2000; Protease-dependent activation of epithelial cells by fungal allergens leads to morphologic changes and cytokine production. J Allergy Clin Immunol 105:1185–1193 [CrossRef]
    [Google Scholar]
  11. Lin S. J., Schranz J., Teutsch S. M. 2001; Aspergillosis case-fatality rate: systematic review of the literature. Clin Infect Dis 32:358–366 [CrossRef]
    [Google Scholar]
  12. Manavathu E. K., Cutright J., Chandrasekar P. H. 1999; Comparative study of susceptibilities of germinated and ungerminated conidia of Aspergillus fumigatus to various antifungal agents. J Clin Microbiol 37:858–861
    [Google Scholar]
  13. Mehrad B., Strieter R. M., Standiford T. J. 1999; Role of TNF- α in pulmonary host defense in murine invasive aspergillosis. J Immunol 162:1633–1640
    [Google Scholar]
  14. Meier A., Kirschning C. J., Nikolaus T., Wagner H., Heesemann J., Ebel F. 2003; Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus -induced activation of murine macrophages. Cell Microbiol 5:561–570 [CrossRef]
    [Google Scholar]
  15. Nissen R. M., Yamamoto K. R. 2000; The glucocorticoid receptor inhibits NF κ B by interfering with serine-2 phosphorylation of the RNA polymerase II carboxy-terminal domain. Genes Dev 14:2314–2329 [CrossRef]
    [Google Scholar]
  16. Phadke A. P., Mehrad B. 2005; Cytokines in host defense against Aspergillus : recent advances. Med Mycol 43 (Suppl. 1):S173–S176 [CrossRef]
    [Google Scholar]
  17. Pylkkanen L., Gullsten H., Majuri M. L., Andersson U., Vanhala E., Maatta J., Meklin T., Hirvonen M. R., Alenius H., Savolainen K. 2004; Exposure to Aspergillus fumigatus spores induces chemokine expression in mouse macrophages. Toxicology 200:255–263 [CrossRef]
    [Google Scholar]
  18. Richardson M. D., Patel M. 1995; Stimulation of neutrophil phagocytosis of Aspergillus fumigatus conidia by interleukin-8 and N -formylmethionyl-leucylphenylalanine. J Med Vet Mycol 33:99–104 [CrossRef]
    [Google Scholar]
  19. Romani L. 2004; Immunity to fungal infections. Nat Rev Immunol 4:1–23 [CrossRef]
    [Google Scholar]
  20. Ruchel R., Margraf S. 1993; Rapid microscopical diagnosis of deep-seated mycoses following maceration of fresh specimens and staining with optical brighteners. Mycoses 36:239–242
    [Google Scholar]
  21. Stephens-Romero S. D., Mednick A. J., Feldmesser M. 2005; The pathogenesis of fatal outcome in murine pulmonary aspergillosis depends on the neutrophil depletion strategy. Infect Immun 73:114–125 [CrossRef]
    [Google Scholar]
  22. Stordeur P., Poulin L. F., Craciun L., Zhou L., Schandene L., de Lavareille A., Goriely S., Goldman M. 2002; Cytokine mRNA quantification by real-time PCR. J Immunol Methods 259:55–64 [CrossRef]
    [Google Scholar]
  23. Tai H. Y., Tam M. F., Chou H., Peng H. J., Su S. N., Perng D. W., Shen H. D. 2006; Pen ch 13 allergen induces secretion of mediators and degradation of occludin protein of human lung epithelial cells. Allergy 61:382–388 [CrossRef]
    [Google Scholar]
  24. Walsh T. J., Roilides E., Cortez K., Kottilil S., Bailey J., Lyman C. A. 2005; Control, immunoregulation, and expression of innate pulmonary host defenses against Aspergillus fumigatus . Med Mycol 43 (Suppl. 1):S165–S172 [CrossRef]
    [Google Scholar]
  25. Wasylnka J. A., Moore M. M. 2002; Uptake of Aspergillus fumigatus conidia by phagocytic and nonphagocytic cells in vitro: quantitation using strains expressing green fluorescent protein. Infect Immun 70:3156–3163 [CrossRef]
    [Google Scholar]
  26. Zhang Z., Liu R., Noordhoek J. A., Kauffman H. F. 2005; Interaction of airway epithelial cells (A549) with spores and mycelium of Aspergillus fumigatus . J Infect 51:375–382 [CrossRef]
    [Google Scholar]
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