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

Didier Salmon*, Gilles Vanwalleghem, Yannick Morias, Julie Denoeud, Carsten Krumbholz, Frédéric Lhommé, Sabine Bachmaier, Markus Kador, Jasmin Gossmann, Fernando Braga Stehling Dias, Géraldine De Muylder, Pierrick Uzureau, Stefan Magez, Muriel Moser, Patrick De Baetselier, Jan Van Den Abbeele, Alain Beschin, Michael Boshart, Etienne Pays

*Corresponding author for this work

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

86 Citations (Scopus)

Abstract

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

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