The local immune response in ulcerative lesions of Buruli disease

Authors

  • A. E. Kiszewski,

    1. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubiràn’, Mexico,
    2. Pathology Section, Graduate and Research Center ‘Prof Heitor Cirne Lima’, FFFCMPA, Porto Alegre, Brazil,
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  • E. Becerril,

    1. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubiràn’, Mexico,
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  • L. D. Aguilar,

    1. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubiràn’, Mexico,
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  • I. T. A. Kader,

    1. Pathology Section, Graduate and Research Center ‘Prof Heitor Cirne Lima’, FFFCMPA, Porto Alegre, Brazil,
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  • W. Myers,

    1. Mycobacteriology Section, Armed Forces Institute of Pathology, Washington, DC, USA, and
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  • F. Portaels,

    1. Mycobacteriology Unit, Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium
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  • R. Hernàndez Pando

    Corresponding author
    1. Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubiràn’, Mexico,
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Dr Rogelio Hernandez Pando, Experimental Pathology Section, Department of Pathology, National Institute of Medical Sciences and Nutrition ‘Salvador Zubiràn’, Vasco de Quiroga 15, Tlalpan, Mexico City, CP-14000, Mexico.
E-mail: rhpando@quetzal.innsz.mx

Summary

Buruli disease (BU) is a progressive necrotic and ulcerative disease of the skin and subcutaneous tissue caused by Mycobacterium ulcerans. BU is considered the third most common mycobacterial disease after tuberculosis and leprosy. Three clinical stages of the cutaneous lesions have been described in BU: pre-ulcerative, ulcerative and healed lesions. In this study we used immunohistochemistry and automated morphometry to determine the percentage of macrophages and of CD4/CD8 lymphocytes and their expression of interferon (IFN)-γ, interleukin (IL)-10, tumour necrosis factor (TNF)-α and transforming growth factor (TGF)-β. Expression of these cytokines was correlated with the inflammatory response evaluated by histopathology. All the studied BU ulcerative cases showed extensive necrosis and chronic inflammation. The most important feature was the presence or absence of granulomas co-existing with a mixed pro-inflammatory/anti-inflammatory cytokine balance. When granulomas were present significantly higher expression of IFN-γ was seen, whereas in ulcerative lesions without granulomas there was increased expression of IL-10 and significantly higher bacillary counts. These features correlated with the chronicity of the lesions; longer-lasting lesions showed granulomas. Thus, granulomas were absent from relatively early ulcerative lesions, which contained more bacilli and little IFN-γ, suggesting that at this stage of the disease strong suppression of the protective cellular immune response facilitates proliferation of bacilli.

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