Aarhus University Seal

Adenylate cyclases of Trypanosoma brucei inhibit the innate immune response of the host

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

DOI

  • Didier Salmon, Université Libre de Bruxelles, Universidade Federal do Rio de Janeiro
  • ,
  • Gilles Vanwalleghem
  • Yannick Morias, Flanders Institute for Biotechnology, Vrije Universiteit Brussel
  • ,
  • Julie Denoeud, Université Libre de Bruxelles
  • ,
  • Carsten Krumbholz, Ludwig Maximilian University of Munich
  • ,
  • Frédéric Lhommé, Center for Microscopy and Molecular Imaging
  • ,
  • Sabine Bachmaier, Ludwig Maximilian University of Munich
  • ,
  • Markus Kador, Ludwig Maximilian University of Munich
  • ,
  • Jasmin Gossmann, Ludwig Maximilian University of Munich
  • ,
  • Fernando Braga Stehling Dias, Université Libre de Bruxelles, Universidade Federal do Rio de Janeiro
  • ,
  • Géraldine De Muylder, Université Libre de Bruxelles
  • ,
  • Pierrick Uzureau, Université Libre de Bruxelles
  • ,
  • Stefan Magez, Vrije Universiteit Brussel, Flanders Institute for Biotechnology
  • ,
  • Muriel Moser, Université Libre de Bruxelles
  • ,
  • Patrick De Baetselier, Flanders Institute for Biotechnology, Vrije Universiteit Brussel
  • ,
  • Jan Van Den Abbeele, Institute of Tropical Medicine Antwerp
  • ,
  • Alain Beschin, Flanders Institute for Biotechnology, Vrije Universiteit Brussel
  • ,
  • Michael Boshart, Ludwig Maximilian University of Munich
  • ,
  • Etienne Pays, Université Libre de Bruxelles, Walloon Excellence in Life Sciences and Biotechnology (WELBIO)

The parasite Trypanosoma brucei possesses a large family of transmembrane receptor-like adenylate cyclases. Activation of these enzymes requires the dimerization of the catalytic domain and typically occurs under stress. Using a dominant-negative strategy, we found that reducing adenylate cyclase activity by about 50% allowed trypanosome growth but reduced the parasite's ability to control the early innate immune defense of the host. Specifically, activation of trypanosome adenylate cyclase resulting from parasite phagocytosis by liver myeloid cells inhibited the synthesis of the trypanosome-controlling cytokine tumor necrosis factor-α through activation of protein kinase A in these cells. Thus, adenylate cyclase activity of lyzed trypanosomes favors early host colonization by live parasites. The role of adenylate cyclases at the host-parasite interface could explain the expansion and polymorphism of this gene family.

Original languageEnglish
JournalScience
Volume337
Issue6093
Pages (from-to)463-466
Number of pages4
ISSN0036-8075
DOIs
Publication statusPublished - 27 Jul 2012
Externally publishedYes

See relations at Aarhus University Citationformats

ID: 221615421