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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/13371

Title: Immunosuppressive Signature of Cutaneous Mycobacterium ulc?rons Infection in the Peripheral Blood of Patients with Buruli Ulcer Disease
Authors: Phillips, Richard
Sarfo, Fred Stephen
Guenin-Mace, Laure
Decalf, Jeremie
Wansbrough-Jones, Mark
Albert, Matthew L.
Demangel, Caroline
Issue Date: 2009
Publisher: The Journal of infectious Diseases
Citation: The Journal of infectious Diseases 2009;200:1675-84
Abstract: Buruli ulcer disease (BUD) is an emerging human disease caused by infection with Mycobacterium ulcerans, which leads to the development of necrotic skin lesions. The pathogenesis of the ulcer is closely associated with the production of mycolactone, a diffusible cytotoxin with immunomodulatory properties. To identify immunological correlates of BUD, we performed a broad screen of inflammatory mediators in serum samples and stimulated whole-blood supernatants of patients. We found that patients with active ulcers displayed a distinctive profile of immune suppression, marked by the down-modulation of selected chemokines and an impaired capacity to produce Thl, Th2, and Thl7 cytokines on stimulation with mitogenic agents. These immunological defects were induced early in the disease and resolved after anti-BUD therapy, establishing their association with the presence of M. ulcerans. Interestingly, some of the defects in cytokine and chemokine response could be mimicked in vitro by incubation of CD4+ peripheral blood lymphocytes with mycolactone. Our findings support the hypothesis that mycolactone contributes to bacterial persistence in human hosts by limiting the generation of adaptive cellular responses. Moreover, we identified immunological markers of BUD, which may be helpful for confirmatory diagnosis of the disease and, especially, for monitoring the response to antibiotic treatment.
Description: An article published in the Journal of infectious Diseases 2009;200:1675-84
URI: http://hdl.handle.net/123456789/13371
Appears in Collections:College of Health Sciences

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