Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host

作者：Salmon Didier^*; Vanwalleghem Gilles; Morias Yannick; Denoeud Julie; Krumbholz Carsten; Lhomme Frederic; Bachmaier Sabine; Kador Markus; Gossmann Jasmin; Dias Fernando Braga Stehling; De Muylder Geraldine; Uzureau Pierrick; Magez Stefan; Moser Muriel; De Baetselier Patrick; Van Den Abbeele Jan; Beschin Alain; Boshart Michael; Pays Etienne

来源：Science, 2012, 337(6093): 463-466.

DOI：10.1126/science.1222753

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%26apos;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.

• 出版日期2012-7-27
• 单位河北医科大学