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Infection and Immunity, January 2005, p. 413-421, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.413-421.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Pasteurella multocida Toxin Activates Human Monocyte-Derived and Murine Bone Marrow-Derived Dendritic Cells In Vitro but Suppresses Antibody Production In Vivo

Kenneth C. Bagley,1,2,{dagger} Sayed F. Abdelwahab,1,3 Robert G. Tuskan,1 and George K. Lewis1,3*

Division of Vaccine Research, Institute of Human Virology, University of Maryland Biotechnology Institute,1 Department of Biochemistry and Molecular Biology,2 Department of Microbiology and Immunology, University of Maryland School of Medicine, University of Maryland Baltimore, Baltimore, Maryland3

Received 12 July 2004/ Returned for modification 26 August 2004/ Accepted 5 September 2004

Pasteurella multocida toxin (PMT) is a potent mitogen for fibroblasts and osteoblastic cells. PMT activates phospholipase C-ß through Gq{alpha}, and the activation of this pathway is responsible for its mitogenic activity. Here, we investigated the effects of PMT on human monocyte-derived dendritic cells (MDDC) in vitro and show a novel activity for PMT. In this regard, PMT activates MDDC to mature in a dose-dependent manner through the activation of phospholipase C and subsequent mobilization of calcium. This activation was accompanied by enhanced stimulation of naïve alloreactive T cells and dominant inhibition of interleukin-12 production in the presence of saturating concentrations of lipopolysaccharide. Surprisingly, although PMT mimics the activating effects of cholera toxin on human MDDC and mouse bone marrow-derived dendritic cells, we found that PMT is not a mucosal adjuvant and that it suppresses the adjuvant effects of cholera toxin in mice. Together, these results indicate discordant effects for PMT in vitro compared to those in vivo.

* Corresponding author. Mailing address: Division of Vaccine Research, Institute of Human Virology, University of Maryland Baltimore, 725 W. Lombard St., Baltimore, MD 21201. Phone: (410) 706-4688. Fax: (410) 706-4695. E-mail: lewisg{at}umbi.umd.edu.

Editor: J. D. Clements

{dagger} Present address: Johns Hopkins Department of Oncology, Baltimore, MD 21231.

Infection and Immunity, January 2005, p. 413-421, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.413-421.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Blocker, D., Berod, L., Fluhr, J. W., Orth, J., Idzko, M., Aktories, K., Norgauer, J. (2006). Pasteurella multocida toxin (PMT) activates RhoGTPases, induces actin polymerization and inhibits migration of human dendritic cells, but does not influence macropinocytosis. Int Immunol 18: 459-464 [Abstract] [Full Text]  


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