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Infection and Immunity, May 2006, p. 2917-2924, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2917-2924.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Cytokine mRNA Expression in Mycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response

R. Phillips,1,2* C. Horsfield,3 J. Mangan,2 K. Laing,2 S. Etuaful,4 P. Awuah,5 K. Nyarko,6 F. Osei-Sarpong,6 P. Butcher,2 S. Lucas,3 and M. Wansbrough-Jones2

Komfo Anokye Teaching Hospital, KNUST, Kumasi, Ghana,1 St. George's University of London, London, United Kingdom,2 St. Thomas' Hospital Campus, Guy's, King's and St. Thomas' School of Medicine, London, United Kingdom,3 St. Martin's Catholic Hospital, Agroyesum, Ghana,4 Nkawie Government Hospital, Nkawie, Ghana,5 Tepa Government Hospital, Tepa, Ghana6

Received 2 August 2005/ Returned for modification 21 September 2005/ Accepted 8 February 2006

Cytokine mRNA expression in biopsies of Mycobacterium ulcerans-infected human tissue was investigated using real-time PCR, and the findings were correlated with the clinical stages of disease and histopathologies. A broad range of cytokine mRNAs were detected in 16 early nodules and 28 late-stage ulcers, including those for the Th1 cytokines tumor necrosis factor alpha (TNF-{alpha}) and gamma interferon (IFN-{gamma}) and the Th2 cytokine interleukin 10 (IL-10). IFN-{gamma} was strongly expressed in both nodules and ulcers, suggesting that a Th1 response begins early in the disease. There was a significantly higher expression of IL-8 and other proinflammatory cytokines in results from 32 biopsies with neutrophilia than in those from 12 biopsies without acute inflammation. Ten tissue samples containing granulomas showed high mRNA expression for IFN-{gamma}, IL-1ß, IL-12p35, IL-12p40, IL-15, and TNF-{alpha} relative to 34 tissue samples without granulomas. These results suggest that the human immune response to M. ulcerans is similar to that seen with some other mycobacteria despite the presence of the toxin mycolactone in the tissues.

* Corresponding author. Mailing address: Department of Infectious Diseases, St. George's University of London, London SW17 ORE, United Kingdom. Phone: 44 208 725 5828. Fax: 44 208 725 3487. E-mail: rphillip{at}sgul.ac.uk.

Editor: J. L. Flynn

Infection and Immunity, May 2006, p. 2917-2924, Vol. 74, No. 5
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.5.2917-2924.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Simmonds, R. E., Lali, F. V., Smallie, T., Small, P. L. C., Foxwell, B. M. (2009). Mycolactone Inhibits Monocyte Cytokine Production by a Posttranscriptional Mechanism. J. Immunol. 182: 2194-2202 [Abstract] [Full Text]  
  • Torrado, E., Adusumilli, S., Fraga, A. G., Small, P. L. C., Castro, A. G., Pedrosa, J. (2007). Mycolactone-Mediated Inhibition of Tumor Necrosis Factor Production by Macrophages Infected with Mycobacterium ulcerans Has Implications for the Control of Infection. Infect. Immun. 75: 3979-3988 [Abstract] [Full Text]  
  • Coutanceau, E., Decalf, J., Martino, A., Babon, A., Winter, N., Cole, S. T., Albert, M. L., Demangel, C. (2007). Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone. JEM 204: 1395-1403 [Abstract] [Full Text]  


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