Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling.

Abstract

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.

• Authors: Silvia Rossi Paccani, Fiorella Tonello, Raffaella Ghittoni, Mariarita Natale, Lucia Muraro, Mario Milco D'Elios, Wei-Jen Tang, Cesare Montecucco, Cosima T Baldari
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 201 Issue 3 Pg. 325-31 (Feb 07 2005) ISSN: 0022-1007 [Print] United States
• PMID: 15699068 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Antigens, CD
• Bacterial Toxins
• Receptors, Antigen
• Transcription Factors
• anthrax toxin

Topics

• Anthrax (immunology)
• Antigens, Bacterial (immunology, metabolism)
• Antigens, CD (immunology)
• Bacillus anthracis (metabolism)
• Bacterial Toxins (immunology)
• Cell Line
• Humans
• Lymphocyte Activation
• Receptors, Antigen (metabolism)
• Signal Transduction (physiology)
• T-Lymphocytes (immunology)
• Transcription Factors (genetics, metabolism)