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Infection and Immunity, February 2010, p. 854-864, Vol. 78, No. 2
0019-9567/10/$12.00+0     doi:10.1128/IAI.01004-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Infection of Mast Cells with Live Streptococci Causes a Toll-Like Receptor 2- and Cell-Cell Contact-Dependent Cytokine and Chemokine Response ^,

Elin Rönnberg,¹ Bengt Guss,² and Gunnar Pejler^1*

Swedish University of Agricultural Sciences, Department of Anatomy, Physiology, and Biochemistry, Uppsala, Sweden,¹ Swedish University of Agricultural Sciences, Department of Microbiology, Uppsala, Sweden²

Received 3 September 2009/ Returned for modification 26 October 2009/ Accepted 11 November 2009

Mast cells (MCs) are strongly implicated in immunity toward bacterial infection, but the molecular mechanisms by which MCs contribute to the host response are only partially understood. We addressed this issue by examining the direct effects of a Gram-positive pathogen, Streptococcus equi, on bone marrow-derived MCs (BMMCs). Ultrastructural analysis revealed extensive formation of dilated rough endoplasmic reticulum in response to bacterial infection, indicating strong induction of protein synthesis. However, the BMMCs did not show signs of extensive degranulation, and this was supported by only slow release of histamine in response to infection. Coculture of live bacteria with BMMCs caused a profound secretion of CCL2/MCP-1, CCL7/MCP-3, CXCL2/MIP-2, CCL5/RANTES, interleukin-4 (IL-4), IL-6, IL-12, IL-13, and tumor necrosis factor alpha, as shown by antibody-based cytokine/chemokine arrays and/or enzyme-linked immunosorbent assay. In contrast, heat-inactivated bacteria caused only minimal cytokine/chemokine release. The cytokine/chemokine responses were substantially attenuated in Toll-like receptor 2-deficient BMMCs and were strongly dependent on cell-cell contacts between bacteria and BMMCs. Gene chip microarray analysis confirmed a massively upregulated expression of the genes coding for the secreted cytokines and chemokines and also identified a pronounced upregulation of numerous additional genes, including transcription factors, signaling molecules, and proteases. Together, the present study outlines MC-dependent molecular events associated with Gram-positive infection and thus provides an advancement in our understanding of how MCs may contribute to host defense toward bacterial insults.

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* Corresponding author. Mailing address: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology, and Biochemistry, BMC, Box 575, SE-75123 Uppsala, Sweden. Phone: 46-18-4714090. Fax: 46-18-550762. E-mail: gunnar.pejler{at}afb.slu.se

Published ahead of print on 23 November 2009.

Supplemental material for this article may be found at http://iai.asm.org/.

Editor: A. J. Bäumler

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Infection and Immunity, February 2010, p. 854-864, Vol. 78, No. 2
0019-9567/10/$12.00+0     doi:10.1128/IAI.01004-09
Copyright © 2010, American Society for Microbiology. All Rights Reserved.