This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Maldonado-Arocho, F. J.
Right arrow Articles by Bradley, K. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Maldonado-Arocho, F. J.
Right arrow Articles by Bradley, K. A.

 Previous Article  |  Next Article 

Infection and Immunity, May 2009, p. 2036-2042, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01329-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Anthrax Edema Toxin Induces Maturation of Dendritic Cells and Enhances Chemotaxis towards Macrophage Inflammatory Protein 3β{triangledown}

Francisco J. Maldonado-Arocho and Kenneth A. Bradley*

Department of Microbiology, Immunology, & Molecular Genetics at University of California, Los Angeles, California 90095

Received 30 October 2008/ Returned for modification 3 December 2008/ Accepted 2 March 2009

Bacillus anthracis secretes two bipartite toxins, edema toxin (ET) and lethal toxin (LT), which impair immune responses and contribute directly to the pathology associated with the disease anthrax. Edema factor, the catalytic subunit of ET, is an adenylate cyclase that impairs host defenses by raising cellular cyclic AMP (cAMP) levels. Synthetic cAMP analogues and compounds that raise intracellular cAMP levels lead to phenotypic and functional changes in dendritic cells (DCs). Here, we demonstrate that ET induces a maturation state in human monocyte-derived DCs (MDDCs) similar to that induced by lipopolysaccharide (LPS). ET treatment results in downregulation of DC-SIGN, a marker of immature DCs, and upregulation of DC maturation markers CD83 and CD86. Maturation of DCs by ET is accompanied by an increased ability to migrate toward the lymph node-homing chemokine macrophage inflammatory protein 3β, like LPS-matured DCs. Interestingly, cotreating with LT differentially affects the ET-induced maturation of MDDCs while not inhibiting ET-induced migration. These findings reveal a mechanism by which ET impairs normal innate immune function and may explain the reported adjuvant effect of ET.

* Corresponding author. Mailing address: Department of Microbiology, Immunology, & Molecular Genetics, University of California at Los Angeles, 609 Charles E. Young Dr. East, Los Angeles, CA 90095. Phone: (310) 206-7465. Fax: (310) 206-5231. E-mail: kbradley{at}microbio.ucla.edu

{triangledown} Published ahead of print on 9 March 2009.

Editor: J. B. Bliska

Infection and Immunity, May 2009, p. 2036-2042, Vol. 77, No. 5
0019-9567/09/$08.00+0     doi:10.1128/IAI.01329-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»