Mycobacterium ulcerans, the cause of Buruli ulcer, is an environmental mycobacterium with a distinct geographic distribution. The reasons why only some individuals who are exposed to M. ulcerans develop ulcers are not known but are likely to reflect individual differences in the immune response to infections with this bacterium. In this study, we investigated cytokine profiles of peripheral blood mononuclear cells (PBMC) from 23 Buruli ulcer patients and 25 household contacts in a region of Australia where Buruli ulcer is endemic. The results showed that following stimulation with M. ulcerans or Mycobacterium bovis BCG, PBMC from Buruli ulcer patients mounted a Th2-type response, which was manifested by the production of mRNA for interleukin 4 (IL-4), IL-5, IL-6, and IL-10, whereas unaffected contacts responded mainly with the Th1 cytokines gamma interferon (IFN-␥) and IL-12. For example, mRNA for IL-4 was detected in 18 of 23 patients but in only 3 of 25 control subjects (P < 0.0001). By contrast, PBMC from 21 of 25 unaffected individuals produced IFN-␥ compared with 3 of 23 patients (P < 0.0001). IFN-␥ release following stimulation with mycobacteria was markedly reduced in affected subjects. Frequencies of antibodies to M. ulcerans in serum samples from affected and unaffected subjects were similar, indicating that many of the control subjects had been exposed to this bacterium. Together, these findings suggest that a Th1-type immune response to M. ulcerans may prevent the development of Buruli ulcer in people exposed to M. ulcerans, but a Th-2 response does not.
We describe a patient with acquired T-helper lymphocyte anergy to mycobacteria following infection with Mycobacterium ulcerans. Before infection, the patient's peripheral blood mononuclear cells responded to in vitro stimulation with M. ulcerans by producing Th1 cytokines, but, after she developed an ulcer, the response was shifted toward production of Th2 cytokines. Immunomodulatory therapy may be an effective intervention for Buruli ulcer.Buruli ulcer is a disease caused by Mycobacterium ulcerans and is the third most common mycobacterial disease in immunocompetent individuals, after tuberculosis and leprosy [1]. In contrast to our knowledge of tuberculosis and leprosy, and despite the frequency of M. ulcerans infection, there is a paucity of knowledge about the human immune response to M. ulcerans. We have recently demonstrated that subjects who develop Buruli ulcer show profound systemic Th1 lymphocyte anergy to M. ulcerans and Mycobacterium bovis [2,3]. Possible explanations for this finding are that subjects who develop Buruli ulcer have an inherent inability to generate a strong Th1 cell response to mycobacterial antigens or that M. ulcerans somehow induces Th1 cell anergy.Patients and methods. We studied the immune response to M. ulcerans in 2 groups of residents in the Douglas Shire of
Background: As the third most common mycobacterial infection in the world after tuberculosis and leprosy, Mycobacterium ulcerans is a major health and development problem that has become the focus of a World Health Organisation (WHO) initiative seeking to reduce the burden of this disease. The Daintree River catchment in north Queensland is an endemic focus for Mycobacterium ulcerans infection, known locally as the 'Daintree Ulcer'. The aim of this study is to analyse the changing pattern of the disease over the last 44 years in the region. Methods: The study is a descriptive review of all human cases where infection had been acquired in an endemic region of far north Queensland. Demographic information, lesion characteristics, management and outcomes were recorded in a database. Results: Over the period there were 92 cases of M. ulcerans infection. The average age was 41.7 years and 56.7% were male. There was distinct clustering of cases in several defined locations in the area. Most cases (90%) presented with ulcers, and all but three patients were treated surgically. Excision and skin grafting was more commonly used in the period between 1964-1988. Excision alone was the most common treatment used thereafter. Earlier recognition and smaller lesion size is thought to have contributed to the change in surgical practice. Conclusions: Ulcers caused by M. ulcerans infection are a distinct clinical entity in tropical North Queensland. Early recognition, diagnosis and prompt surgical intervention has minimised morbidity associated with this disease.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.