Differential production of systemic and intralesional gamma interferon and interleukin-10 in nodular and ulcerative forms of Buruli disease.

Buruli disease, caused by Mycobacterium ulcerans, is the third most important mycobacterial disease in humans besides tuberculosis and leprosy. We have compared systemic and intralesional cytokine production in patients presenting with a nodular form and a necrotizing, ulcerative form of the disease. Gamma interferon (IFN-gamma) levels in response to whole M. ulcerans and Mycobacterium bovis BCG bacilli and in response to purified Ag85 protein from BCG were lower in peripheral blood mononuclear cells (PBMC) cultures from Buruli disease patients than in PBMC from healthy purified protein derivative-positive contacts. Interleukin-4 (IL-4) and IL-13 content was below the detection threshold in these PBMC cultures. IFN-gamma production after stimulation with M. ulcerans was significantly lower (P < 0.05) in PBMC cultures from patients with ulcers than in those from patients with nodules. On the other hand, PBMC from Buruli disease patients produced significant levels of IL-10 in response to M. ulcerans (but not to M. bovis BCG) and production was highest in patients with the ulcerative form. Third, semiquantitative reverse transcription-PCR analysis demonstrated a similar difference in the local, intralesional cytokine profile for the two forms of the disease: high IFN-gamma but low IL-10 mRNA levels in nodular lesions and high IL-10 but low IFN-gamma mRNA levels in ulcerative lesions. Intralesional IL-4 and IL-13 mRNA levels were low and only detected in patients with the ulcerative form. Our results indicate, although they do not formally prove, that production of IL-10 rather than production of IL-4 or IL-13 by Th2-type T cells may be involved in the low M. ulcerans-specific IFN-gamma response in Buruli disease patients.

American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis coinfection with downregulation of the T-helper 1 cell response.

Cutaneous leishmaniasis, leprosy, and tuberculosis are caused by intracellular pathogens whose development depends on impaired cell-mediated immunity. We report an exceptional triple association of American cutaneous leishmaniasis, lepromatous leprosy, and pulmonary tuberculosis in a man with no recognized immunodeficiency. Normal immunological assessment of the interferon-gamma pathway does not support the hypothesis of a genetic defect in any of the genes involved in the T helper (Th)-1 cytokine cascade in this patient. Unresponsiveness to interleukin (IL)-12 of his T cells after stimulation with Leishmania guyanensis, Mycobacterium bovis bacille Calmette-Guérin, and Mycobacterium leprae antigens suggested the inability to mount an appropriate Th cell response to upregulate the IL-12 receptor expression.