Phagocytosis of<i>Mycobacterium ulcerans</i>in the course of rifampicin and streptomycin chemotherapy in Buruli ulcer lesions

Schütte, Daniela; UmBoock, A.; Pluschke, Gerd

doi:10.1111/j.1365-2133.2008.08879.x

Cited by 38 publications

(53 citation statements)

References 27 publications

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“…This may be partially explained by the fact that systemic suppression of cellular responses in patients with BUD is incomplete and reversible. Although Th1 responses are signifi- cantly impaired in patients with BUD, particularly during the early stages of the disease, host T cells remain viable and functional as the disease progresses, as evidenced by the vigorous inflammation occurring in the skin after antibiotic administration [31][32][33]. The success of M. ulcerans in the establishment of a persistent infection may thus be viewed as a balance between pathogen and host, in which mycolactone suppresses but does not neutralize the development of host immune responses.…”

Section: Discussionmentioning

confidence: 96%

Immunosuppressive Signature of CutaneousMycobacterium ulceransInfection in the Peripheral Blood of Patients with Buruli Ulcer Disease

et al. 2009

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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.

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Section: Discussionmentioning

confidence: 96%

Immunosuppressive Signature of CutaneousMycobacterium ulceransInfection in the Peripheral Blood of Patients with Buruli Ulcer Disease

et al. 2009

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“…These may emerge from globi-like accumulations of AFB originating from bacteria that were internalized and transported to distant sites by phagocytic cells. Globi-like accumulations are also found in human BU [43] and in experimentally infected mice [44]–[46]. Again, these microcolonies may have to reach a critical size to be able to develop a protective cloud of mycolactone around them.…”

Section: Discussionmentioning

confidence: 99%

Experimental Infection of the Pig with Mycobacterium ulcerans: A Novel Model for Studying the Pathogenesis of Buruli Ulcer Disease

Bolz

Ruggli²,

Ruf

et al. 2014

PLoS Negl Trop Dis

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BackgroundBuruli ulcer (BU) is a slowly progressing, necrotising disease of the skin caused by infection with Mycobacterium ulcerans. Non-ulcerative manifestations are nodules, plaques and oedema, which may progress to ulceration of large parts of the skin. Histopathologically, BU is characterized by coagulative necrosis, fat cell ghosts, epidermal hyperplasia, clusters of extracellular acid fast bacilli (AFB) in the subcutaneous tissue and lack of major inflammatory infiltration. The mode of transmission of BU is not clear and there is only limited information on the early pathogenesis of the disease available.Methodology/Principal FindingsFor evaluating the potential of the pig as experimental infection model for BU, we infected pigs subcutaneously with different doses of M. ulcerans. The infected skin sites were excised 2.5 or 6.5 weeks after infection and processed for histopathological analysis. With doses of 2×107 and 2×106 colony forming units (CFU) we observed the development of nodular lesions that subsequently progressed to ulcerative or plaque-like lesions. At lower inoculation doses signs of infection found after 2.5 weeks had spontaneously resolved at 6.5 weeks. The observed macroscopic and histopathological changes closely resembled those found in M. ulcerans disease in humans.Conclusion/SignificanceOur results demonstrate that the pig can be infected with M. ulcerans. Productive infection leads to the development of lesions that closely resemble human BU lesions. The pig infection model therefore has great potential for studying the early pathogenesis of BU and for the development of new therapeutic and prophylactic interventions.

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“…[38][39][40] Paradoxical reactions probably result from antibiotic-mediated killing of 41,42 Clinically, this reaction manifests as a deterioration of the lesion or its surrounding tissues or the appearance of new lesions, either locally or in a distant body site. [38][39][40]43 Paradoxical reactions pose notable management challenges in resource-poor settings because of the absence of available diagnostic testing to distinguish them from treatment failure, which is diffi cult on clinical criteria alone.…”

Section: Paradoxical Reactions To Antibiotic Treatmentmentioning

confidence: 99%

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa

O’Brien¹,

Comte²,

Serafini³

et al. 2014

The Lancet Infectious Diseases

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Phagocytosis ofMycobacterium ulceransin the course of rifampicin and streptomycin chemotherapy in Buruli ulcer lesions

Cited by 38 publications

References 27 publications

Immunosuppressive Signature of CutaneousMycobacterium ulceransInfection in the Peripheral Blood of Patients with Buruli Ulcer Disease

Immunosuppressive Signature of CutaneousMycobacterium ulceransInfection in the Peripheral Blood of Patients with Buruli Ulcer Disease

Experimental Infection of the Pig with Mycobacterium ulcerans: A Novel Model for Studying the Pathogenesis of Buruli Ulcer Disease

The urgent need for clinical, diagnostic, and operational research for management of Buruli ulcer in Africa

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