Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host
Adenylate Cyclases of Trypanosoma brucei Inhibit the Innate Immune Response of the Host
复制标题
DOI：
10.1126/science.1222753
复制
发表时间：
2012-07-27
期刊：
影响因子：
56.9
通讯作者：
Pays, Etienne
中科院分区：
文献类型：
--
作者：
Salmon, Didier;Vanwalleghem, Gilles;Pays, Etienne
寄生虫布鲁氏锥虫具有一个大家族的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，通常发生在压力下。使用显性阴性策略，我们发现将腺苷酸环化酶活性降低约50%可以使锥虫生长，但降低了寄生虫控制宿主早期先天免疫防御的能力。具体来说，由寄生虫吞噬引起的肝髓细胞激活锥虫腺苷酸环化酶，通过激活这些细胞中的蛋白激酶A，抑制了锥虫控制细胞因子肿瘤坏死因子- α的合成。因此，被分解的锥虫的腺苷酸环化酶活性有利于活寄生虫在宿主的早期定植。腺苷酸环化酶在宿主-寄生虫界面上的作用可以解释该基因家族的扩展和多态性。
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.