Theses / Dissertations >
College of Health Sciences >
Please use this identifier to cite or link to this item:
|Title: ||Immunosuppressive Signature of Cutaneous Mycobacterium ulcerans Infection in the Peripheral Blood of Patients with Buruli Ulcer Disease|
|Authors: ||Phillips, Richard O.|
Sarfo, Fred S.
Albert, Matthew L.
|Issue Date: ||28-Oct-2009|
|Publisher: ||Infectious Diseases Society of America|
|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 Th1, Th2, and Th17 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 by Infectious Diseases Society of America and is available at DOI: 10.1086/646615|
|Appears in Collections:||College of Health Sciences|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.