Downregulation of Mitogen-Activated Protein Kinases by theBordetella bronchisepticaType III Secretion System Leads to Attenuated Nonclassical Macrophage Activation

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Abstract
Bordetella bronchisepticautilizes a type III secretion system (TTSS) to establish a persistent infection of the murine respiratory tract. Previous studies have shown that theBordetellaTTSS mediated cytotoxicity in different cell types, inhibition of NF-κB 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 theBordetellaTTSS. 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 theBordetellaTTSS. In dendritic cells, ERK was transiently activated, but this failed to alter cytokine profiles. These results suggest that theBordetellaTTSS 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.