Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling.
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.
Paccani
Silvia Rossi
SR
Department of Evolutionary Biology, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy.
Tonello
Fiorella
F
Ghittoni
Raffaella
R
Natale
Mariarita
M
Muraro
Lucia
L
D'Elios
Mario Milco
MM
Tang
Wei-Jen
WJ
Montecucco
Cesare
C
Baldari
Cosima T
CT
D000881:Anthrax / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology; D001408:Bacillus anthracis / Q000378:metabolism; D001427:Bacterial Toxins / Q000276:immunology*; D002460:Cell Line; D006801:Humans; D008213:Lymphocyte Activation; D011946:Receptors, Antigen / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D000942:Antigens, Bacterial; D015703:Antigens, CD; D001427:Bacterial Toxins; D011946:Receptors, Antigen; D014157:Transcription Factors; C030325:anthrax toxin