Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus

*Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129;
^†Boston Biomedical Research Institute, Watertown, MA 02472;
^‡Ben-May Institute for Cancer Research, University of Chicago, Chicago, IL 60637; and
^§Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115

Edited by Michael Karin, University of California at San Diego School of Medicine, La Jolla, CA, and approved March 6, 2008 (received for review January 4, 2008)

Abstract

Bacillus anthracis, the etiologic agent of anthrax, avoids immune surveillance and commandeers host macrophages as a vehicle for lymphatic spreading. Here, we show that B. anthracis edema toxin (ET), via its adenylyl cyclase activity, dramatically increases the motility of infected macrophages and the expression of vascular endothelial growth factor. The transcription factor CREB and the syndecan-1 gene, a CREB target, play crucial roles in ET-induced macrophage migration. These molecular and cellular responses occur in macrophages engaged in antiinflammatory G protein-coupled receptor activation, thus illustrating a common signaling circuitry controlling resolution of inflammation and host cell hijacking by B. anthracis.

Footnotes

^¶To whom correspondence should be addressed. E-mail: jmpark{at}cbrc2.mgh.harvard.edu
Author contributions: C.K., S.W.-A., R.J.C., and J.M.P. designed research; C.K., S.W.-A., Y.S., and J.M.P. performed research; W.-J.T. and R.J.C. contributed new reagents/analytic tools; C.K., S.W.-A., and J.M.P. analyzed data; and C.K., S.W.-A., and J.M.P. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: The data reported in this paper have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE9184).
This article contains supporting information online at www.pnas.org/cgi/content/full/0800105105/DCSupplemental.