publication . Article . 2007

Selective suppression of dendritic cell functions by Mycobacterium ulcerans toxin mycolactone.

Nathalie WINTER; Caroline Demangel;
Open Access
  • Published: 11 Jun 2007 Journal: Journal of Experimental Medicine, volume 204, pages 1,395-1,403 (issn: 0022-1007, eissn: 1540-9538, Copyright policy)
  • Publisher: Rockefeller University Press
International audience; Mycolactone is a polyketide toxin produced by Mycobacterium ulcerans (Mu), the causative agent of the skin disease Buruli ulcer (BU). Surprisingly, infected tissues lack inflammatory infiltrates. Structural similarities between mycolactone and immunosuppressive agents led us to investigate the immunomodulatory properties of mycolactone on dendritic cells (DCs), the key initiators and regulators of immune responses. At noncytotoxic concentrations, phenotypic and functional maturation of both mouse and human DCs was inhibited by mycolactone. Notably, mycolactone blocked the emigration of mouse-skin DCs to draining lymph nodes, as well as th...
free text keywords: Immunology, Immunology and Allergy, Articles, Article, POLYKETIDE TOXIN, CHEMOKINES, INTERFERON, BURULI ULCER, IMMUNE-RESPONSE, MACROLIDE TOXIN, INFECTION, TUBERCULOSIS, EXPRESSION, EVOLUTION, [SDV.IMM]Life Sciences [q-bio]/Immunology, Microbiologie et Parasitologie, Microbiology and Parasitology, BURULI ULCER;IMMUNE-RESPONSE;POLYKETIDE TOXIN;MACROLIDE TOXIN;INFECTION;CHEMOKINES;TUBERCULOSIS;INTERFERON;EXPRESSION;EVOLUTION, mycotoxine, interleukine, cellule dendritique, mycobacterium, réponse immunitaire
Funded by
NIH| Mycolactone-Mediated Virulence in M. ulcerans
  • Funder: National Institutes of Health (NIH)
  • Project Code: 5R01AI049418-03
NIH| TB Research Materials and Vaccine testing-26675320
  • Funder: National Institutes of Health (NIH)
  • Project Code: N01AI075320-009
35 references, page 1 of 3

1. Wansbrough-Jones, M., and R. Phillips. 2006. Buruli ulcer: emerging from obscurity. Lancet. 367:1849-1858.

2. George, K.M., D. Chatterjee, G. Gunawardana, D. Welty, J. Hayman, R. Lee, and P.L.C. Small. 1999. Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence. Science. 283:854-857.

3. Coutanceau, E., L. Marsollier, R. Brosch, E. Perret, P. Goossens, M. Tanguy, S.T. Cole, P.L.C. Small, and C. Demangel. 2005. Modulation of the host immune response by a transient intracellular stage of Mycobacterium ulcerans: the contribution of endogenous mycolactone toxin. Cell. Microbiol. 7:1187-1196.

4. Guarner, J., J. Bartlett, E.A.S. Whitney, P.L. Raghunathan, Y. Stienstra, K. Asamoa, S. Etuaful, E. Klutse, E. Quarshie, T.S. van der Werf, et al. 2003. Histopathologic features of Mycobacterium ulcerans infection. Emerg. Infect. Dis. 9:651-656. [OpenAIRE]

5. Oliveira, M.S., 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. 2005. Infection with Mycobacterium ulcerans induces persistent infl ammatory responses in mice. Infect. Immun. 73:6299-6310.

6. Phillips, R., C. Horsefild, J. Mangan, K. Laing, S. Etuaful, P. Awuah, K. Nyarko, F. Osei-Sarpong, P. Butcher, S. Lucas, and M. WansbroughJones. 2006. Cytokine mRNA expression in Mycobacterium ulceransinfected human skin and correlation with local infl ammatory response. Infect. Immun. 74:2917-2924.

7. Prevot, G., E. Bourreau, H. Pascalis, R. Pradinaud, A. Tanghe, K. Huygen, and P. Launois. 2004. Dif erential production of systemic and intralesional IFN-γ and IL-10 in nodular and ulcerative forms of Buruli disease. Infect. Immun. 72:958-965.

8. Gooding, T.M., P.D.R. Johnson, D.E. Campbell, J.A. Hayman, E.L. Hartland, A.S. Kemp, and R.M. Robins-Browne. 2001. Immune response to infection with Mycobacterium ulcerans. Infect. Immun. 69:1704-1707. [OpenAIRE]

9. Gooding, T.M., P.D.R. Johnson, M. Smith, A.S. Kemp, and R.M. Robins-Browne. 2002. Cytokine profiles of patients infected with Mycobacterium ulcerans and unaf ected household contacts. Infect. Immun. 70:5562-5567.

10. Gooding, T.M., A.S. Kemp, R.M. Robins-Browne, M. Smith, and P.D.R. Johnson. 2003. Acquired T-helper 1 lymphocyte anergy following infection with Mycobacterium ulcerans. Clin. Infect. Dis. 36:1076-1077.

11. Westenbrink, B.D., 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. 2005. Cytokine responses to stimulation of whole blood from patients with Buruli ulcer disease in Ghana. Clin. Diagn. Lab. Immunol. 12:125-129. [OpenAIRE]

12. Yeboah-Manu, D., E. Peduzzi, E. Mensah-Quainoo, A. Asante-Poku, D. Ofori-Adjei, G. Pluschke, and C.A. Daubenberger. 2006. Systemic suppression of IFN-γ responses in Buruli ulcer patients resolves after surgical excision of the lesions caused by the extracellular pathogen Mycobacterium ulcerans. J. Leukoc. Biol. 79:1150-1156. [OpenAIRE]

13. Belkaid, Y., H. Jouin, and G. Milon. 1996. A method to recover, enumerate and identify lymphomyeloid cells present in an infl ammatory dermal site: a study in laboratory mice. J. Immunol. Methods. 199:5-25.

14. Mve-Obiang, A., R.E. Lee, E.S. Umstot, K.A. Trott, T.C. Grammer, J.M. Parker, B.S. Ranger, R. Grainger, E.A. Mahrous, and P.L.C. Small. 2005. A newly discovered mycobacterial pathogen isolated from laboratory colonies of Xenopus species with lethal infections produces a novel form of mycolactone, the Mycobacterium ulcerans macrolide toxin. Infect. Immun. 73:3307-3312. [OpenAIRE]

15. Ranger, B.S., E.A. Mahrous, L. Mosi, S. Adusumilli, R.E. Lee, A. Colorni, M. Rhodes, and P.L.C. Small. 2006. Globally distributed mycobacterial fi sh pathogens produce a novel plasmid-encoded toxic macrolide, mycolactone F. Infect. Immun. 74:6037-6045. [OpenAIRE]

35 references, page 1 of 3
Powered by OpenAIRE Research Graph
Any information missing or wrong?Report an Issue