Bacillus anthracis: a multi-faceted role for anthrax lethal toxin in thwarting host immune defenses.
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.
Xu
Lixin
L
Division of Monoclonal Antibodies, Center for Drug Evaluation and Research, United States Food and Drug Administration, Building 29B, Room 3NN22, Bethesda, MD 20892, USA.
Frucht
David M
DM
D000818:Animals; D000881:Anthrax / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism; D001408:Bacillus anthracis / Q000201:enzymology / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000276:immunology*; D045726:Metalloproteases / Q000276:immunology* / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D020929:Mitogen-Activated Protein Kinase Kinases; D045726:Metalloproteases