Xu Lixin, Frucht David M
Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, United States Food and Drug Administration, Building 29B, Room 3NN22, Bethesda, MD 20892, USA.
Int J Biochem Cell Biol. 2007;39(1):20-4. doi: 10.1016/j.biocel.2006.08.010. Epub 2006 Sep 1.
Lethal factor (LF), along with its receptor-binding partner protective antigen (PA), forms lethal toxin (LT), a critical virulence factor for Bacillus anthracis. LF is a Zn(2+) protease that cleaves specific mitogen activated protein kinase kinases (MAPKKs), inactivating signal transduction intermediates required for normal immune function. Initial research emphasized the role of LT in attenuating pro-inflammatory responses by macrophages, the primary targets of infection. More recent studies have revealed that LT affects a broad range of immune cells. In addition to direct effects on macrophages and neutrophils, LT suppresses the costimulatory functions of dendritic cells, thereby impeding essential cross-talk between innate and adaptive immune responses. Moreover, LT acts directly on T and B lymphocytes, blocking antigen receptor-dependent proliferation, cytokine production and Ig production. In this manner, LT mounts a broad-based attack on host immunity, thus providing B. anthracis with multiple mechanisms for avoiding protective host responses.
致死因子（LF）与其受体结合伴侣保护性抗原（PA）形成致死毒素（LT），这是炭疽芽孢杆菌的一种关键毒力因子。LF是一种锌离子蛋白酶，可切割特定的丝裂原活化蛋白激酶激酶（MAPKKs），使正常免疫功能所需的信号转导中间体失活。最初的研究强调了LT在减弱巨噬细胞（感染的主要靶细胞）促炎反应中的作用。最近的研究表明，LT会影响广泛的免疫细胞。除了对巨噬细胞和中性粒细胞有直接作用外，LT还会抑制树突状细胞的共刺激功能，从而阻碍先天免疫和适应性免疫反应之间的重要相互作用。此外，LT直接作用于T淋巴细胞和B淋巴细胞，阻断抗原受体依赖性增殖、细胞因子产生和免疫球蛋白产生。通过这种方式，LT对宿主免疫进行广泛攻击，从而为炭疽芽孢杆菌提供了多种避免宿主保护性反应的机制。
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