This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lindgren, H.
Right arrow Articles by Sjöstedt, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lindgren, H.
Right arrow Articles by Sjöstedt, A.

 Previous Article  |  Next Article 

Infection and Immunity, December 2004, p. 7172-7182, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7172-7182.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Distinct Roles of Reactive Nitrogen and Oxygen Species To Control Infection with the Facultative Intracellular Bacterium Francisella tularensis

Helena Lindgren,1,2 Stephan Stenmark,1,2 Wangxue Chen,3 Arne Tärnvik,2 and Anders Sjöstedt1*

Department of Clinical Microbiology, Clinical Bacteriology,1 Infectious Diseases, Umeå University, Umeå, Sweden,2 National Research Council Canada, Institute for Biological Sciences, Ottawa, Canada3

Received 24 March 2004/ Returned for modification 14 June 2004/ Accepted 2 September 2004

Reactive nitrogen species (RNS) and reactive oxygen species (ROS) are important mediators of the bactericidal host response. We investigated the contribution of these two mediators to the control of infection with the facultative intracellular bacterium Francisella tularensis. When intradermally infected with the live vaccine strain F. tularensis LVS, mice deficient in production of RNS (iNOS–/– mice) or in production of ROS by the phagocyte oxidase (p47phox–/– mice) showed compromised resistance to infection. The 50% lethal dose (LD50) for iNOS–/– mice was <20 CFU, and the LD50 for p47phox–/– mice was 4,400 CFU, compared to an LD50 of >500,000 CFU for wild-type mice. The iNOS–/– mice survived for 26.4 ± 1.8 days, and the p47phox–/– mice survived for 10.1 ± 1.3 days. During the course of infection, the serum levels of gamma interferon (IFN-{gamma}) and interleukin-6 were higher in iNOS–/– and p47phox–/– mice than in wild-type mice. Histological examination of livers of iNOS–/– mice revealed severe liver pathology. Splenocytes obtained 5 weeks after primary infection from antibiotic-treated iNOS–/– mice showed an in vitro recall response that was similar in magnitude and greater secretion of IFN-{gamma} compared to cells obtained from wild-type mice. In summary, mice lacking expression of RNS or ROS showed extreme susceptibility to infection with F. tularensis LVS. The roles of RNS and ROS seemed to be distinct since mice deficient in production of ROS showed dissemination of infection and died during the early phase of infection, whereas RNS deficiency led to severe liver pathology and a contracted course of infection.

* Corresponding author. Mailing address: Department of Clinical Microbiology, Clinical Bacteriology, Umeå University, SE-901 85 Umeå, Sweden. Phone: 46-90-7851120. Fax: 46-90-7852225. E-mail: Anders.Sjostedt{at}climi.umu.se.

Editor: A. D. O'Brien

Infection and Immunity, December 2004, p. 7172-7182, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.7172-7182.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mahawar, M., Kirimanjeswara, G. S., Metzger, D. W., Bakshi, C. S. (2009). Contribution of Citrulline Ureidase to Francisella tularensis Strain Schu S4 Pathogenesis. J. Bacteriol. 191: 4798-4806 [Abstract] [Full Text]  
  • Collazo, C. M., Meierovics, A. I., De Pascalis, R., Wu, T. H., Lyons, C. R., Elkins, K. L. (2009). T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria. Infect. Immun. 77: 2010-2021 [Abstract] [Full Text]  
  • Couper, K. N., Lanthier, P. A., Perona-Wright, G., Kummer, L. W., Chen, W., Smiley, S. T., Mohrs, M., Johnson, L. L. (2009). Anti-CD25 Antibody-Mediated Depletion of Effector T Cell Populations Enhances Susceptibility of Mice to Acute but Not Chronic Toxoplasma gondii Infection. J. Immunol. 182: 3985-3994 [Abstract] [Full Text]  
  • Vojtech, L. N., Sanders, G. E., Conway, C., Ostland, V., Hansen, J. D. (2009). Host Immune Response and Acute Disease in a Zebrafish Model of Francisella Pathogenesis. Infect. Immun. 77: 914-925 [Abstract] [Full Text]  
  • Mares, C. A., Ojeda, S. S., Morris, E. G., Li, Q., Teale, J. M. (2008). 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. Infect. Immun. 76: 3001-3010 [Abstract] [Full Text]  
  • Guina, T., Radulovic, D., Bahrami, A. J., Bolton, D. L., Rohmer, L., Jones-Isaac, K. A., Chen, J., Gallagher, L. A., Gallis, B., Ryu, S., Taylor, G. K., Brittnacher, M. J., Manoil, C., Goodlett, D. R. (2007). MglA Regulates Francisella tularensis subsp. novicida (Francisella novicida) Response to Starvation and Oxidative Stress. J. Bacteriol. 189: 6580-6586 [Abstract] [Full Text]  
  • Baron, S. D., Singh, R., Metzger, D. W. (2007). Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion. Infect. Immun. 75: 2152-2162 [Abstract] [Full Text]  
  • Lindgren, H., Shen, H., Zingmark, C., Golovliov, I., Conlan, W., Sjostedt, A. (2007). Resistance of Francisella tularensis Strains against Reactive Nitrogen and Oxygen Species with Special Reference to the Role of KatG. Infect. Immun. 75: 1303-1309 [Abstract] [Full Text]  
  • Scorpio, D. G., von Loewenich, F. D., Gobel, H., Bogdan, C., Dumler, J. S. (2006). Innate Immune Response to Anaplasma phagocytophilum Contributes to Hepatic Injury.. CVI 13: 806-809 [Abstract] [Full Text]  
  • Barker, J. H., Weiss, J., Apicella, M. A., Nauseef, W. M. (2006). Basis for the Failure of Francisella tularensis Lipopolysaccharide To Prime Human Polymorphonuclear Leukocytes.. Infect. Immun. 74: 3277-3284 [Abstract] [Full Text]  
  • Cole, L. E., Elkins, K. L., Michalek, S. M., Qureshi, N., Eaton, L. J., Rallabhandi, P., Cuesta, N., Vogel, S. N. (2006). Immunologic Consequences of Francisella tularensis Live Vaccine Strain Infection: Role of the Innate Immune Response in Infection and Immunity.. J. Immunol. 176: 6888-6899 [Abstract] [Full Text]  
  • Mariathasan, S., Weiss, D. S., Dixit, V. M., Monack, D. M. (2005). Innate immunity against Francisella tularensis is dependent on the ASC/caspase-1 axis. JEM 202: 1043-1049 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»