Anthrax toxins inhibit immune cell chemotaxis by perturbing chemokine receptor signalling.
Pathogenic strains of Bacillus anthracis produce two potent toxins, lethal toxin (LT), a metalloprotease that cleaves mitogen-activated protein kinase kinases, and oedema toxin (ET), a calcium/calmodulin-dependent adenylate cyclase. Emerging evidence indicates a role for both toxins in suppressing the initiation of both innate and adaptive immune responses, which are essential to keep the infection under control. Here we show that LT and ET inhibit chemotaxis of T-cells and macrophages by subverting signalling by both CXC and CC chemokine receptors. The data highlight a novel strategy of immunosuppression by B. anthracis based on inhibition of immune cell homing.
Rossi Paccani
Silvia
S
Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy.
Tonello
Fiorella
F
Patrussi
Laura
L
Capitani
Nagaja
N
Simonato
Morena
M
Montecucco
Cesare
C
Baldari
Cosima T
CT
D000942:Antigens, Bacterial / Q000494:pharmacology*; D001408:Bacillus anthracis / Q000378:metabolism; D001427:Bacterial Toxins / Q000494:pharmacology*; D002478:Cells, Cultured; D054405:Chemokine CCL3; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D048369:MAP Kinase Kinase 1 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D019707:Receptors, Chemokine / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C515429:CCL3 protein, human; C515255:CXCL12 protein, human; D054405:Chemokine CCL3; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019707:Receptors, Chemokine; C030325:anthrax toxin; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D020929:Mitogen-Activated Protein Kinase Kinases