Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling
Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling
复制标题
DOI：
10.1084/jem.20041557
复制
发表时间：
2005-02-07
影响因子：
15.3
通讯作者：
Baldari, CT
中科院分区：
文献类型：
--
作者：
Paccani, SR;Tonello, F;Baldari, CT
炭疽是由炭疽杆菌的致病菌株引起的感染，其分泌由保护性抗原（PA）、水肿因子（EF）和致死因子（LF）组成的三组分毒性复合物。PA与LF或EF形成二元复合物并介导它们进入宿主细胞。虽然细菌生长的初始阶段发生在淋巴结中，但宿主未能产生有效的免疫应答。在这里，我们表明，LT和ET是通过抗原受体触发的人T细胞活化和增殖的有效抑制剂。LT和ET均抑制促分裂原活化蛋白和应激激酶途径，并且两种毒素均抑制细胞因子基因表达所必需的两种转录因子NFAT和AP-1的活化。这些数据确定了B的免疫逃避的新策略。炭疽，基于毒性复合物的两个效应子单位，并针对获得性免疫的关键细胞成分。
Anthrax is an infection caused by pathogenic strains of Bacillus anthracis, which secretes a three-component toxic complex consisting of protective antigen (PA), edema factor (EF), and lethal factor (LF). PA forms binary complexes with either LF or EF and mediates their entry into host cells. Although the initial phases of bacterial growth occur in the lymph node, the host fails to mount an effective immune response. Here, we show that LT and ET are potent suppressors of human T cell activation and proliferation triggered through the antigen receptor. Both LT and ET inhibit the mitogen-activated protein and stress kinase pathways, and both toxins inhibit activation of NFAT and AP-1, two transcription factors essential for cytokine gene expression. These data identify a novel strategy of immune evasion by B. anthracis, based on both effector subunits of the toxic complex, and targeted to a key cellular component of adaptive immunity.