Laboratory of Molecular Parasitology, Institute for Molecular Biology and Medicine, Université Libre de Bruxelles, 12, rue des Professeurs Jeener et Brachet, B6041 Gosselies, Belgium.
Science. 2012 Jul 27;337(6093):463-6. doi: 10.1126/science.1222753. Epub 2012 Jun 14.
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.
寄生虫布氏锥虫拥有一大类跨膜受体样腺苷酸环化酶。这些酶的激活需要催化结构域的二聚化，通常在应激下发生。我们使用显性负性策略发现，通过将腺苷酸环化酶活性降低约 50%，可以允许锥虫生长，但降低了寄生虫控制宿主早期固有免疫防御的能力。具体而言，寄生虫被肝髓样细胞吞噬后产生的锥虫腺苷酸环化酶的激活通过在这些细胞中激活蛋白激酶 A 抑制了控制锥虫的细胞因子肿瘤坏死因子-α的合成。因此，裂解的锥虫的腺苷酸环化酶活性有利于活寄生虫对宿主的早期定植。在宿主-寄生虫界面上，腺苷酸环化酶的作用可以解释该基因家族的扩张和多态性。
