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Infection and Immunity, July 2008, p. 3001-3010, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00215-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Initial Delay in the Immune Response to Francisella tularensis Is Followed by Hypercytokinemia Characteristic of Severe Sepsis and Correlating with Upregulation and Release of Damage-Associated Molecular Patterns{triangledown}

Chris A. Mares,1 Sandra S. Ojeda,1 Elizabeth G. Morris,2 Qun Li,2 and Judy M. Teale1,2*

Department of Microbiology and Immunology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229,1 South Texas Center for Emerging Infectious Diseases and Department of Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, Texas 782492

Received 15 January 2008/ Returned for modification 27 March 2008/ Accepted 4 April 2008

"Francisella tularensis subsp. novicida" intranasal infection causes a rapid pneumonia in mice with mortality at 4 to 6 days with a low dose of bacteria (102 bacteria). The short time to death suggests that there is a failure of the innate immune response. As the neutrophil is often the first cell type to infiltrate sites of infection, we focused on the emigration of neutrophils in this infection, as well as cytokines involved in their recruitment. The results indicated that there was a significant delay in the influx of neutrophils into the bronchoalveolar lavage fluid of F. tularensis subsp. novicida-infected mice. The delay in neutrophil recruitment in F. tularensis subsp. novicida-infected mice correlated with a delay in the upregulation of multiple proinflammatory cytokines and chemokines, as well as a delay in caspase-1 activation. Strikingly, the initial delay in the upregulation of cytokines through 1 day postinfection was followed by profound upregulation of multiple cytokines and chemokines to levels consistent with hypercytokinemia described for severe sepsis. This finding was further supported by a bacteremia and the cellular relocalization and release of high-mobility group box-1 and S100A9, both of which are damage-associated molecular pattern molecules and are known to be mediators of severe sepsis.

* Corresponding author. Mailing address: Department of Biology, The University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249-1644. Phone: (210) 458-7024. Fax: (210) 458-7025. E-mail: judy.teale{at}utsa.edu

{triangledown} Published ahead of print on 14 April 2008.

Editor: A. J. Bäumler

Infection and Immunity, July 2008, p. 3001-3010, Vol. 76, No. 7
0019-9567/08/$08.00+0     doi:10.1128/IAI.00215-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Sharma, J., Li, Q., Mishra, B. B., Georges, M. J., Teale, J. M. (2009). Vaccination with an Attenuated Strain of Francisella novicida Prevents T-Cell Depletion and Protects Mice Infected with the Wild-Type Strain from Severe Sepsis. Infect. Immun. 77: 4314-4326 [Abstract] [Full Text]  
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