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Infection and Immunity, November 2007, p. 5338-5345, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00561-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Toll-Like Receptor 2 Controls the Gamma Interferon Response to Francisella tularensis by Mouse Liver Lymphocytes{triangledown}

Kee-Jong Hong,1,{dagger} Jason R. Wickstrum,1,{dagger} Hung-Wen Yeh,2 and Michael J. Parmely1*

Department of Microbiology, Molecular Genetics and Immunology,1 Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas 661602

Received 18 April 2007/ Returned for modification 19 June 2007/ Accepted 25 August 2007

The production of gamma interferon (IFN-{gamma}) is a key step in the protective innate immune response to Francisella tularensis. Natural killer cells and T cells in the liver are important sources of this cytokine during primary F. tularensis infections, and interleukin-12 (IL-12) appears to be an essential coactivating cytokine for hepatic IFN-{gamma} expression. The present study was undertaken to determine whether or not macrophages (M{phi}) or dendritic cells (DC) provide coactivating signals for the liver IFN-{gamma} response in vitro, whether IL-12 mediates these effects, and whether Toll-like receptor (TLR) signaling is essential to induce this costimulatory activity. Both bone marrow-derived M{phi} and DC significantly augmented the IFN-{gamma} response of F. tularensis-challenged liver lymphocytes in vitro. While both cell types produced IL-12p40 in response to F. tularensis challenge, only DC secreted large quantities of IL-12p70. DC from both IL-12p35-deficient and TLR2-deficient mice failed to produce IL-12p70 and did not costimulate liver lymphocytes for IFN-{gamma} production in response to viable F. tularensis organisms. Conversely, liver lymphocytes from TLR2-deficient mice cocultured with wild-type accessory cells produced IFN-{gamma} at levels comparable to those for wild-type hepatic lymphocytes. These findings indicate that TLR2 controls hepatic lymphocyte IFN-{gamma} responses to F. tularensis by regulating DC IL-12 production. While M{phi} also coinduced hepatic IFN-{gamma} production in response to F. tularensis, they did so in a fashion less dependent on TLR2.

* Corresponding author. Mailing address: Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160. Phone: (913) 588-7053. Fax: (913) 588-7295. E-mail: mparmely{at}kumc.edu

{triangledown} Published ahead of print on 4 September 2007.

Editor: J. L. Flynn

{dagger} These authors contributed equally to this study.

Infection and Immunity, November 2007, p. 5338-5345, Vol. 75, No. 11
0019-9567/07/$08.00+0     doi:10.1128/IAI.00561-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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