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Infection and Immunity, January 2005, p. 308-316, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.308-316.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Downregulation of Mitogen-Activated Protein Kinases by the Bordetella bronchiseptica Type III Secretion System Leads to Attenuated Nonclassical Macrophage Activation

Annette Reissinger, Jason A. Skinner, and Ming H. Yuk*

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania

Received 10 July 2004/ Returned for modification 19 August 2004/ Accepted 24 September 2004

Bordetella bronchiseptica utilizes a type III secretion system (TTSS) to establish a persistent infection of the murine respiratory tract. Previous studies have shown that the Bordetella TTSS mediated cytotoxicity in different cell types, inhibition of NF-{kappa}B in epithelial cells, and differentiation of dendritic cells into a semimature state. Here we demonstrate modulation of mitogen-activated protein kinase (MAPK) signaling pathways and altered cytokine production in macrophages and dendritic cells by the Bordetella TTSS. In macrophages, the MAPKs ERK and p38 were downregulated. This resulted in attenuated production of interleukin- (IL-)6 and IL-10. In contrast, the Th-1-polarizing cytokine IL-12 was produced at very low levels and remained unmodulated by the Bordetella TTSS. In dendritic cells, ERK was transiently activated, but this failed to alter cytokine profiles. These results suggest that the Bordetella TTSS modulates antigen-presenting cells in a cell type-specific manner and the secretion of high levels of IL-6 and IL-10 by macrophages might be important for pathogen clearance.

* Corresponding author. Mailing address: Department of Microbiology, University of Pennsylvania School of Medicine, 201C Johnson Pavilion, 3610 Hamilton Walk, Philadelphia, PA 19104-6084. Phone: (215) 573-6690. Fax: (215) 273-4184. E-mail: mingy{at}mail.med.upenn.edu.

Editor: J. B. Bliska

Infection and Immunity, January 2005, p. 308-316, Vol. 73, No. 1
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.1.308-316.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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