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. Althou...
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| Published in: | The Journal of experimental medicine Vol. 201; no. 3; pp. 325 - 331 |
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| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
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07-02-2005
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| 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. |
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| AbstractList | 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. 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. |
| Author | Natale, Mariarita Montecucco, Cesare Baldari, Cosima T D'Elios, Mario Milco Tonello, Fiorella Muraro, Lucia Tang, Wei-Jen Ghittoni, Raffaella Paccani, Silvia Rossi |
| AuthorAffiliation | 5 Ben-May Institute for Cancer Research, University of Chicago, Chicago, IL 60637 2 Department of Clinical Medicine and Immunological Sciences, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy 1 Department of Evolutionary Biology, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy 3 Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy 4 Department of Internal Medicine and Immunoallergology, University of Florence, 50134 Florence, Italy |
| AuthorAffiliation_xml | – name: 5 Ben-May Institute for Cancer Research, University of Chicago, Chicago, IL 60637 – name: 3 Department of Biomedical Sciences, University of Padua, 35121 Padua, Italy – name: 4 Department of Internal Medicine and Immunoallergology, University of Florence, 50134 Florence, Italy – name: 2 Department of Clinical Medicine and Immunological Sciences, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy – name: 1 Department of Evolutionary Biology, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy |
| Author_xml | – sequence: 1 givenname: Silvia Rossi surname: Paccani fullname: Paccani, Silvia Rossi organization: Department of Evolutionary Biology, Policlinico Le Scotte, University of Siena, 53100 Siena, Italy – sequence: 2 givenname: Fiorella surname: Tonello fullname: Tonello, Fiorella – sequence: 3 givenname: Raffaella surname: Ghittoni fullname: Ghittoni, Raffaella – sequence: 4 givenname: Mariarita surname: Natale fullname: Natale, Mariarita – sequence: 5 givenname: Lucia surname: Muraro fullname: Muraro, Lucia – sequence: 6 givenname: Mario Milco surname: D'Elios fullname: D'Elios, Mario Milco – sequence: 7 givenname: Wei-Jen surname: Tang fullname: Tang, Wei-Jen – sequence: 8 givenname: Cesare surname: Montecucco fullname: Montecucco, Cesare – sequence: 9 givenname: Cosima T surname: Baldari fullname: Baldari, Cosima T |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/15699068$$D View this record in MEDLINE/PubMed |
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| Copyright | Copyright © 2005, The Rockefeller University Press |
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| Snippet | Anthrax is an infection caused by pathogenic strains of Bacillus anthracis, which secretes a three-component toxic complex consisting of protective antigen... Anthrax is an infection caused by pathogenic strains of Bacillus anthracis , which secretes a three-component toxic complex consisting of protective antigen... |
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| SubjectTerms | Anthrax - immunology Antigens, Bacterial - immunology Antigens, Bacterial - metabolism Antigens, CD - immunology Bacillus anthracis Bacillus anthracis - metabolism Bacterial Toxins - immunology Brief Definitive Report Cell Line Humans Lymphocyte Activation Receptors, Antigen - metabolism Signal Transduction - physiology T-Lymphocytes - immunology Transcription Factors - genetics Transcription Factors - metabolism |
| Title | Anthrax toxins suppress T lymphocyte activation by disrupting antigen receptor signaling |
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