| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
B Function1
*
Infectious Diseases and Microbiology, Charing Cross Campus, Imperial College, London, United Kingdom;
Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; and
Cytokine Biology and Signal Transduction Laboratory, Kennedy Institute of Rheumatology, London, United Kingdom
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-
B activation.
Surprisingly, a synergy was observed between the factor and phorbol
ester-directed NF-B activation. The factor had no effect on IL-1- or
LPS-induced NF-B activity, indicating selective activity of the
factor. The factor did not inhibit the degradation of IB
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.
This article has been cited by other articles:
|
|
 |
|
  E. Torrado, S. Adusumilli, A. G. Fraga, P. L. C. Small, A. G. Castro, and J. Pedrosa Mycolactone-Mediated Inhibition of Tumor Necrosis Factor Production by Macrophages Infected with Mycobacterium ulcerans Has Implications for the Control of Infection Infect. Immun., August 1, 2007; 75(8): 3979 - 3988. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Coutanceau, J. Decalf, A. Martino, A. Babon, N. Winter, S. T. Cole, M. L. Albert, and C. Demangel Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone J. Exp. Med., June 11, 2007; 204(6): 1395 - 1403. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yeboah-Manu, E. Peduzzi, E. Mensah-Quainoo, A. Asante-Poku, D. Ofori-Adjei, G. Pluschke, and C. A. Daubenberger Systemic suppression of interferon-{gamma} responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans J. Leukoc. Biol., June 1, 2006; 79(6): 1150 - 1156. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Phillips, C. Horsfield, J. Mangan, K. Laing, S. Etuaful, P. Awuah, K. Nyarko, F. Osei-Sarpong, P. Butcher, S. Lucas, et al. Cytokine mRNA Expression in Mycobacteriam ulcerans-Infected Human Skin and Correlation with Local Inflammatory Response. Infect. Immun., May 1, 2006; 74(5): 2917 - 2924. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Oliveira, A. G. Fraga, E. Torrado, A. G. Castro, J. P. Pereira, A. L. Filho, F. Milanezi, F. C. Schmitt, W. M. Meyers, F. Portaels, et al. Infection with Mycobacterium ulcerans Induces Persistent Inflammatory Responses in Mice Infect. Immun., October 1, 2005; 73(10): 6299 - 6310. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. WALSH, W. M. MEYERS, F. PORTAELS, J. E. LANE, D. MONGKOLSIRICHAIKUL, K. HUSSEM, P. GOSI, and K. S. A. MYINT HIGH RATES OF APOPTOSIS IN HUMAN MYCOBACTERIUM ULCERANS CULTURE-POSITIVE BURULI ULCER SKIN LESIONS Am J Trop Med Hyg, August 1, 2005; 73(2): 410 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. P. Stinear, H. Hong, W. Frigui, M. J. Pryor, R. Brosch, T. Garnier, P. F. Leadlay, and S. T. Cole Common Evolutionary Origin for the Unstable Virulence Plasmid pMUM Found in Geographically Diverse Strains of Mycobacterium ulcerans J. Bacteriol., March 1, 2005; 187(5): 1668 - 1676. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Westenbrink, Y. Stienstra, M. G. Huitema, W. A. Thompson, E. O. Klutse, E. O. Ampadu, H. M. Boezen, P. C. Limburg, and T. S. van der Werf Cytokine Responses to Stimulation of Whole Blood from Patients with Buruli Ulcer Disease in Ghana Clin. Vaccine Immunol., January 1, 2005; 12(1): 125 - 129. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Guizani-Tabbane, K. Ben-Aissa, M. Belghith, A. Sassi, and K. Dellagi Leishmania major Amastigotes Induce p50/c-Rel NF-{kappa}B Transcription Factor in Human Macrophages: Involvement in Cytokine Synthesis Infect. Immun., May 1, 2004; 72(5): 2582 - 2589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. N. Okenu, L. O. Ofielu, K. A. Easley, J. Guarner, E. A. Spotts Whitney, P. L. Raghunathan, Y. Stienstra, K. Asamoa, T. S. van der Werf, W. T. A. van der Graaf, et al. Immunoglobulin M Antibody Responses to Mycobacterium ulcerans Allow Discrimination between Cases of Active Buruli Ulcer Disease and Matched Family Controls in Areas Where the Disease Is Endemic Clin. Vaccine Immunol., March 1, 2004; 11(2): 387 - 391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Prevot, E. Bourreau, H. Pascalis, R. Pradinaud, A. Tanghe, K. Huygen, and P. Launois Differential Production of Systemic and Intralesional Gamma Interferon and Interleukin-10 in Nodular and Ulcerative Forms of Buruli Disease Infect. Immun., February 1, 2004; 72(2): 958 - 965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Portaels, J. Aguiar, M. Debacker, C. Steunou, C. Zinsou, A. Guedenon, and W. M. Meyers Prophylactic Effect of Mycobacterium bovis BCG Vaccination against Osteomyelitis in Children with Mycobacterium ulcerans Disease (Buruli Ulcer) Clin. Vaccine Immunol., November 1, 2002; 9(6): 1389 - 1391. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Gooding, P. D. R. Johnson, M. Smith, A. S. Kemp, and R. M. Robins-Browne Cytokine Profiles of Patients Infected with Mycobacterium ulcerans and Unaffected Household Contacts Infect. Immun., October 1, 2002; 70(10): 5562 - 5567. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Caamano and C. A. Hunter NF-{kappa}B Family of Transcription Factors: Central Regulators of Innate and Adaptive Immune Functions Clin. Microbiol. Rev., July 1, 2002; 15(3): 414 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Tato and C. A. Hunter Host-Pathogen Interactions: Subversion and Utilization of the NF-{kappa}B Pathway during Infection Infect. Immun., July 1, 2002; 70(7): 3311 - 3317. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Mason, J. Aliberti, J. C. Caamano, H.-C. Liou, and C. A. Hunter Cutting Edge: Identification of c-Rel-Dependent and -Independent Pathways of IL-12 Production During Infectious and Inflammatory Stimuli J. Immunol., March 15, 2002; 168(6): 2590 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. A. Pahlevan, D. J. M. Wright, L. Bradley, C. Smith, and B. M. J. Foxwell Potential of rifamides to inhibit TNF-induced NF-{kappa}B activation J. Antimicrob. Chemother., March 1, 2002; 49(3): 531 - 534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Dobos, P. L. Small, M. Deslauriers, F. D. Quinn, and C. H. King Mycobacterium ulcerans Cytotoxicity in an Adipose Cell Model Infect. Immun., November 1, 2001; 69(11): 7182 - 7186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Gooding, P. D. R. Johnson, D. E. Campbell, J. A. Hayman, E. L. Hartland, A. S. Kemp, and R. M. Robins-Browne Immune Response to Infection with Mycobacterium ulcerans Infect. Immun., March 1, 2001; 69(3): 1704 - 1707. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. George, L. Pascopella, D. M. Welty, and P. L. C. Small A Mycobacterium ulcerans Toxin, Mycolactone, Causes Apoptosis in Guinea Pig Ulcers and Tissue Culture Cells Infect. Immun., February 1, 2000; 68(2): 877 - 883. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
