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The Inhibitory Action of Mycobacterium ulcerans Soluble Factor on Monocyte/T Cell Cytokine Production and NF-κB Function

Authors :
Ali A. Pahlevan
David J. M. Wright
Caroline Andrews
Kathleen M. George
Pamela L. C. Small
Brian M. Foxwell
Source :
The Journal of Immunology. 163:3928-3935
Publication Year :
1999
Publisher :
The American Association of Immunologists, 1999.

Abstract

Buruli ulcer is a chronic and progressive necrotizing ulcer for which there is no medical treatment. Historically, a soluble toxin (factor) derived from the causative Mycobacterium ulcerans was found to induce the massive necrosis of skin and s.c. tissue seen in this condition. However, the persistence of the disease is thought to be caused by a lack of any immune response. We therefore investigated whether the factor was related to immunosuppression. A protocol to partially purify the factor was developed, and its effects on immune competent cells were tested. The factor produced >95% inhibition of LPS-induced release of TNF and IL-10 from human monocytes and caused a loss of adherence of these cells without cell death. The factor also blocked the production of IL-2 from activated T lymphocytes. The factor had no effect on TNF-induced cytotoxicity, but abrogated TNF-induced NF-κB activation. Surprisingly, a synergy was observed between the factor and phorbol ester-directed NF-κB activation. The factor had no effect on IL-1- or LPS-induced NF-κB activity, indicating selective activity of the factor. The factor did not inhibit the degradation of IκBα induced by TNF, indicating that the target for its activity lies within an undefined part of the TNF signaling mechanism. The data indicate that the localized immunosuppression associated with Buruli ulcer relates to the activity of the released factor, and this may provide a target for future therapeutic strategies for this intractable disease.

Subjects

Subjects :
Immunology
Immunology and Allergy

Details

ISSN :
15506606 and 00221767
Volume :
163
Database :
OpenAIRE
Journal :
The Journal of Immunology
Accession number :
edsair.doi...........c44c43c4d025cfc2f8f6c6f939449dd3
Full Text :
https://doi.org/10.4049/jimmunol.163.7.3928