This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.00200-08v1 76/7/2822    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Paccani, S. R. Articles by Baldari, C. T. PubMed PubMed Citation Articles by Paccani, S. R. Articles by Baldari, C. T.

 Previous Article  |  Next Article 

Infection and Immunity, July 2008, p. 2822-2832, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00200-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Suppression of T-Lymphocyte Activation and Chemotaxis by the Adenylate Cyclase Toxin of Bordetella pertussis

Department of Evolutionary Biology, University of Siena, Via Aldo Moro 2, 53100 Siena, Italy,¹ Department of Biomedical Sciences, University of Padua, Via Trieste 75, 35121 Padua, Italy,² Department of Internal Medicine and Immunoallergology, University of Florence, Viale Morgagni 85, 50134 Florence, Italy,³ CNRS URA 2185, Department of Structural Biology and Chemistry, Institut Pasteur, 75724 Paris Cedex 15, France⁴

Received 13 February 2008/ Returned for modification 17 March 2008/ Accepted 7 April 2008

The adenylate cyclase toxin (CyaA) released by Bordetella pertussis is an essential virulence factor for colonization of the host. This toxin inhibits migration and activation of phagocytes, thereby preventing bacterial killing. In addition, CyaA interferes with the initiation of adaptive immunity by misdirecting dendritic cell differentiation to a suppressive rather than stimulatory phenotype. Here we show that CyaA directly affects adaptive responses by catalyzing cyclic AMP (cAMP) production in peripheral blood lymphocytes. Treatment with CyaA resulted in profound impairment of T-lymphocyte activation and chemotaxis. These effects resulted from inhibition of T-cell antigen receptor and chemokine receptor signaling via a cAMP/protein kinase A (PKA)-dependent pathway. A comparison of the activities of CyaA on T-cell and macrophage activation and migration revealed that the biological effects of the toxin were paralleled by inhibition of the activation of mitogen-activated protein (MAP) kinases, highlighting the conclusion that the ubiquitous and evolutionarily conserved MAP kinase modules are common targets of the PKA-mediated immunosuppressant activities of CyaA and underlining the potential of cAMP-elevating toxins as a means of evasion of immunity by bacterial pathogens.

Published ahead of print on 21 April 2008.

Editor: S. R. Blanke