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Int J Biochem Cell Biol. 2007;39(1):20-4. Epub 2006 Sep 1.

Bacillus anthracis: a multi-faceted role for anthrax lethal toxin in thwarting host immune defenses.

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Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, United States Food and Drug Administration, Building 29B, Room 3NN22, Bethesda, MD 20892, USA.


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.

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