Journal
SCIENCE
Volume 337, Issue 6093, Pages 463-466Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1222753
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Funding
- Belgian Fund for Scientific Research (FRSM)
- Wallonie-Bruxelles International/Fundacao Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)
- Jean Brachet Fund
- Interuniversity Attraction Poles Programme-Belgian Science Policy
- German Research Foundation (DFG) [1100/7-1]
- University of Munich
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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-alpha 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.
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