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Infection and Immunity, June 2008, p. 2439-2447, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00115-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Innate Immune Response to Salmonella enterica Serovar Typhimurium by Macrophages Is Dependent on TREM2-DAP12{triangledown}

Julia F. Charles,1,2 Mary Beth Humphrey,1,2,{dagger} Xiaodan Zhao,3 Ellen Quarles,3 Mary C. Nakamura,1,2 Alan Aderem,4 William E. Seaman,1,2 and Kelly D. Smith3*

Department of Medicine, University of California—San Francisco, San Francisco, California 94143,1 Medical Service, Veteran's Administration Medical Center, San Francisco, California 94121,2 Department of Pathology, University of Washington, Seattle, Washington,3 Institute for Systems Biology, Seattle, Washington4

Received 26 January 2008/ Returned for modification 20 February 2008/ Accepted 28 March 2008

Macrophage recognition of Salmonella enterica serovar Typhimurium leads to a cascade of signaling events, including the activation of Src family and Syk kinases and the production of reactive oxygen species (ROS), which are critical for host innate defense during early stages of bacterial infection. ROS production depends on the NADPH oxidase, but little is known about the innate immune receptors and proximal adapters that regulate Salmonella-induced ROS. Herein, we demonstrate that serovar Typhimurium induces ROS through a pathway that requires both triggering receptor expressed on myeloid cells 2 (TREM2) and DAP12. This pathway is highly analogous to the pathways utilized by Fc receptors and integrins to regulate ROS production. Oral infection of mice with serovar Typhimurium demonstrates that the DAP12-dependent pathway regulates cecal colonization during early stages of Salmonella infection. Thus, DAP12 is an important regulator of Salmonella-induced ROS production in macrophages, and TREM2 is essential for linking DAP12 to the innate response to serovar Typhimurium.

* Corresponding author. Mailing address: Department of Pathology, University of Washington, Box 357470, 1959 NE Pacific St., Seattle, WA 98195. Phone: (206) 543-0820. Fax: (206) 598-4928. E-mail: kelsmith{at}u.washington.edu

{triangledown} Published ahead of print on 7 April 2008.

Editor: B. A. McCormick

{dagger} Present address: Department of Medicine, Oklahoma University Health Sciences Center, Oklahoma City, OK 73104.

Infection and Immunity, June 2008, p. 2439-2447, Vol. 76, No. 6
0019-9567/08/$08.00+0     doi:10.1128/IAI.00115-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • N'Diaye, E.-N., Branda, C. S., Branda, S. S., Nevarez, L., Colonna, M., Lowell, C., Hamerman, J. A., Seaman, W. E. (2009). TREM-2 (triggering receptor expressed on myeloid cells 2) is a phagocytic receptor for bacteria. JCB 184: 215-223 [Abstract] [Full Text]  


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