the adenylate cyclase toxins of bacillus anthracis and bordetella pertussis promote th2 cell development by shaping t cell antigen receptor signaling腺苷酸环化酶毒素的炭疽杆菌和百日咳博德特氏菌促进th2细胞发展塑造t细胞抗原受体信号.pdf

The Adenylate Cyclase Toxins of Bacillus anthracis and Bordetella pertussis Promote Th2 Cell Development by Shaping T Cell Antigen Receptor Signaling 1 2 1 3 4 Silvia Rossi Paccani , Marisa Benagiano , Nagaja Capitani , Irene Zornetta , Daniel Ladant , Cesare 3 2 1 Montecucco , Mario M. D’Elios , Cosima T. Baldari * 1 Department of Evolutionary Biology, University of Siena, Siena, Italy, 2 Department of Internal Medicine and Immunoallergology, University of Florence, Florence, Italy, ´ ´ 3 Department of Biomedical Sciences, University of Padua, Padua, Italy, 4 Unite de Biochimie des Interactions Macromoleculaires, CNRS URA 2185, Institut Pasteur, Paris, France Abstract The adjuvanticity of bacterial adenylate cyclase toxins has been ascribed to their capacity, largely mediated by cAMP, to modulate APC activation, resulting in the expression of Th2–driving cytokines. On the other hand, cAMP has been demonstrated to induce a Th2 bias when present during T cell priming, suggesting that bacterial cAMP elevating toxins may directly affect the Th1/Th2 balance. Here we have investigated the effects on human CD4+ T cell differentiation of two adenylate cyclase toxins, Bacillus anthracis edema toxin (ET) and Bordetella pertussis CyaA, which differ in structure, mode of cell entry, and subcellular localization. We show that low concentrations of ET and CyaA, but not of their genetically detoxified adenylate cyclase defective counterparts, potently promote Th2 cell differentiation by inducing e