Systemic and local interferon-gamma production following Mycobacterium ulcerans infection
M. G. Huitema
Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, and
Search for more papers by this authorP. C. Limburg
Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, and
Search for more papers by this authorCorresponding Author
T. S. Van Der Werf
Departments of Internal Medicine,
T. S. van der Werf, Infectious diseases Service and Tuberculosis Unit, University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB Groningen, the Netherlands.E-mail: [email protected]Search for more papers by this authorM. G. Huitema
Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, and
Search for more papers by this authorP. C. Limburg
Immunology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands, and
Search for more papers by this authorCorresponding Author
T. S. Van Der Werf
Departments of Internal Medicine,
T. S. van der Werf, Infectious diseases Service and Tuberculosis Unit, University Medical Center Groningen, University of Groningen, PO Box 30 001, 9700 RB Groningen, the Netherlands.E-mail: [email protected]Search for more papers by this authorSummary
Buruli ulcer disease (BUD) is an emerging predominantly tropical disease caused by Mycobacterium ulcerans. The initial pre-ulcerative skin lesion often breaks down into an ulcer with undermined edges. Healing is common but may require considerable time, and scarring often results in functional limitations. Considerable evidence has now emerged that patients with early BUD cannot mount a sufficient protective T helper 1 (Th1) cell response to M. ulcerans, but uncertainty remains as to whether immune protection is restored over time. This study investigates the Th1 cell response of patients with various stages of BUD on mycobacterial antigens. We measured interferon (IFN)-γ levels after ex vivo whole blood stimulation with tuberculin purified protein derivative (PPD), and compared the Th1 cell response of individuals with pre-ulcerative, ulcerative and healed BUD as well as healthy controls. Moreover, the systemic Th1 cell response was related to histopathological features in the various stages of surgically resected BUD lesions. We show that patients with ulcerative and healed BUD produce significantly higher IFN-γ levels after mycobacterial ex vivo whole blood stimulation than healthy controls, and that patients with a granulomatous tissue response produce higher IFN-γ levels than individuals without. We therefore suggest that the mounted Th1 cell response in ulcerative BUD patients might be related to their histopathological tissue response.
References
- 1 Van Der Werf TS, Stienstra Y, Johnson RC et al. Mycobacterium ulcerans disease. Bull World Health Organ 2005; 83: 785–91.
- 2 Stinear T, Davies JK, Jenkin GA, Hayman JA, Oppedisano F, Johnson PD. Identification of Mycobacterium ulcerans in the environment from regions in Southeast Australia in which it is endemic with sequence capture-PCR. Appl Environ Microbiol 2000; 66: 3206–13.
- 3 Marsollier L, Robert R, Aubry J et al. Aquatic insects as a vector for Mycobacterium ulcerans. Appl Environ Microbiol 2002; 68: 4623–8.
- 4 Marsollier L, Severin T, Aubry J et al. Aquatic snails, passive hosts of Mycobacterium ulcerans. Appl Environ Microbiol 2004; 70: 6296–8.
- 5 Hayman J. Out of Africa: observations on the histopathology of Mycobacterium ulcerans infection. J Clin Pathol 1993; 46: 5–9.
- 6 Wansbrough-Jones M, Phillips R. Buruli ulcer: emerging from obscurity. Lancet 2006; 367: 1849–58.
- 7 Stienstra Y, Dijkstra PU, Guedenon A et al. Development of a questionnaire assessing Buruli ulcer-induced functional limitation. Am J Trop Med 2004; 70: 318–22.
- 8 Revill WD, Morrow RH, Pike MC, Ateng J. A controlled trial of the treatment of Mycobacterium ulcerans infection with clofazimine. Lancet 1973; 2: 873–7.
- 9 Amofah G, Asamoah S, Afram-Gyening C. Effectiveness of excision of pre-ulcerative Buruli lesions in field situations in a rural district in Ghana. Trop Doct 1998; 28: 81–3.
- 10 Chauty A, Ardant MF, Adeye A et al. Promising clinical efficacy of the combination streptomycin–rifampin for the treatment of Buruli ulcer (Mycobacterium ulcerans disease). Antimicrob Agents Chemother 2007; [Epub ahead of print] doi: 10.1128/ACC.00175-17.
- 11 Okenu DM, Ofielu LO, Easley KA et al. Immunoglobulin M antibody responses to Mycobacterium ulcerans allow discrimination between cases of active Buruli ulcer disease and matched family controls in areas where the disease is endemic. Clin Diagn Lab Immunol 2004; 11: 387–91.
- 12 Stanford JL, Revill WD, Gunthorpe WJ, Grange JM. The production and preliminary investigation of Burulin, a new skin test reagent for Mycobacterium ulcerans infection. J Hyg (Lond) 1975; 74: 7–16.
- 13 Dobos KM, Spotts EA, Marston BJ, Horsburgh CR Jr, King CH. Serologic response to culture filtrate antigens of Mycobacterium ulcerans during Buruli ulcer disease. Emerg Infect Dis 2000; 6: 158–64.
- 14 Westenbrink BD, Stienstra Y, Huitema MG et al. Cytokine responses to stimulation of whole blood from patients with Buruli ulcer disease in Ghana. Clin Diagn Lab Immunol 2005; 12: 125–9.
- 15 Phillips R, Horsfield C, Kuijper S et al. Cytokine response to antigen stimulation of whole blood from patients with Mycobacterium ulcerans disease compared to that from patients with tuberculosis. Clin Vaccine Immunol 2006; 13: 253–7.
- 16 Yeboah-Manu D, Peduzzi E, Mensah-Quainoo E et al. Systemic suppression of interferon-gamma responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans. J Leukoc Biol 2006; 79: 1150–6.
- 17 Kiszewski AE, Becerril E, Aguilar LD et al. The local immune response in ulcerative lesions of Buruli disease. Clin Exp Immunol 2006; 143: 445–51.
- 18 Phillips R, Horsfield C, Mangan J et al. Cytokine mRNA expression in Mycobacterium ulcerans-infected human skin and correlation with local inflammatory response. Infect Immun 2006; 74: 2917–24.
- 19 Gooding TM, Johnson PD, Campbell DE et al. Immune response to infection with Mycobacterium ulcerans. Infect Immun 2001; 69: 1704–7.
- 20 Gooding TM, Johnson PD, Smith M, Kemp AS, Robins-Browne RM. Cytokine profiles of patients infected with Mycobacterium ulcerans and unaffected household contacts. Infect Immun 2002; 70: 5562–7.
- 21 Prévot G, Bourreau E, Pascalis H et al. Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease. Infect Immun 2004; 72: 958–65.
- 22 Popa ER, Franssen CF, Limburg PC, Huitema MG, Kallenberg CG, Tervaert JW. In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase. Arthritis Rheum 2002; 46: 1894–904.
- 23 Guarner J, Bartlett J, Whitney EA et al. Histopathologic features of Mycobacterium ulcerans infection. Emerg Infect Dis 2003; 9: 651–6.
- 24 Portaels F, Aguiar J, Debacker M et al. Mycobacterium bovis BCG vaccination as prophylaxis against Mycobacterium ulcerans osteomyelitis in Buruli ulcer disease. Infect Immun 2004; 72: 62–5.
- 25 Nackers F, Dramaix M, Johnson RC et al. BCG vaccine effectiveness against Buruli ulcer: a case–control study in Benin. Am J Trop Med 2006; 75: 768–74.
- 26 Debacker M, Aguiar J, Steunou C et al. Mycobacterium ulcerans disease (Buruli ulcer) in rural hospital, Southern Benin, 1997–2001. Emerg Infect Dis 2004; 10: 1391–8.
- 27 Gooding TM, Kemp AS, Robins-Browne RM, Smith M, Johnson PD. Acquired T-helper 1 lymphocyte anergy following infection with Mycobacterium ulcerans. Clin Infect Dis 2003; 36: 1076–7.
- 28 Stienstra Y, Van Der Graaf WT, Asamoa K, Van Der Werf TS. Beliefs and attitudes toward Buruli ulcer in Ghana. Am J Trop Med 2002; 67: 207–13.
- 29 Aujoulat I, Johnson C, Zinsou C, Guedenon A, Portaels F. Psychosocial aspects of health seeking behaviours of patients with Buruli ulcer in southern Benin. Trop Med Int Health 2003; 8: 750–9.
- 30 Mve-Obiang A, Lee RE, Portaels F, Small PL. Heterogeneity of mycolactones produced by clinical isolates of Mycobacterium ulcerans: implications for virulence. Infect Immun 2003; 71: 774–83.
- 31 Portaels F, Fonteyene PA, De Beenhouwer H et al. Variability in 3′ end of 16S rRNA sequence of Mycobacterium ulcerans is related to geographic origin of isolates. J Clin Microbiol 1996; 34: 962–5.
- 32 Sahiratmadja E, Alisjahbana B, De Boer T et al. Dynamic changes in pro- and anti-inflammatory cytokine profiles and gamma interferon receptor signaling integrity correlate with tuberculosis disease activity and response to curative treatment. Infect Immun 2007; 75: 820–9.
