Antiinflammatory cAMP signaling and cell migration genes co-opted by the anthrax bacillus.
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.
Kim
Chun
C
Cutaneous Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129, USA.
Wilcox-Adelman
Sarah
S
Sano
Yasuyo
Y
Tang
Wei-Jen
WJ
Collier
R John
RJ
Park
Jin Mo
JM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000881:Anthrax / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D000942:Antigens, Bacterial / Q000378:metabolism; D001408:Bacillus anthracis / Q000201:enzymology*; D001427:Bacterial Toxins / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005786:Gene Expression Regulation; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D015398:Signal Transduction; D053668:Syndecan-1 / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D043562:Receptors, G-Protein-Coupled; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D042461:Vascular Endothelial Growth Factor A; C030325:anthrax toxin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases