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 Google Scholar
Google Scholar
Right arrow Articles by Vojtech, L. N.
Right arrow Articles by Hansen, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vojtech, L. N.
Right arrow Articles by Hansen, J. D.

 Previous Article  |  Next Article 

Infection and Immunity, February 2009, p. 914-925, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01201-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Host Immune Response and Acute Disease in a Zebrafish Model of Francisella Pathogenesis{triangledown}

Lucia N. Vojtech,1,2 George E. Sanders,2,3 Carla Conway,2 Vaughn Ostland,4 and John D. Hansen1,2*

Interdisciplinary Program in Pathobiology, University of Washington, Seattle, Washington 98195,1 U.S. Geological Survey, Western Fisheries Research Center, Seattle, Washington 98115,2 Department of Comparative Medicine, University of Washington, Seattle, Washington 98195,3 Kent SeaTech Corporation, San Diego, California 921214

Received 26 September 2008/ Returned for modification 7 November 2008/ Accepted 24 November 2008

Members of the bacterial genus Francisella are highly virulent and infectious pathogens. New models to study Francisella pathogenesis in evolutionarily distinct species are needed to provide comparative insight, as the mechanisms of host resistance and pathogen virulence are not well understood. We took advantage of the recent discovery of a novel species of Francisella to establish a zebrafish/Francisella comparative model of pathogenesis and host immune response. Adult zebrafish were susceptible to acute Francisella-induced disease and suffered mortality in a dose-dependent manner. Using immunohistochemical analysis, we localized bacterial antigens primarily to lymphoid tissues and livers of zebrafish following infection by intraperitoneal injection, which corresponded to regions of local cellular necrosis. Francisella sp. bacteria replicated rapidly in these tissues beginning 12 h postinfection, and bacterial titers rose steadily, leveled off, and then decreased by 7 days postinfection. Zebrafish mounted a significant tissue-specific proinflammatory response to infection as measured by the upregulation of interleukin-1β (IL-1β), gamma interferon, and tumor necrosis factor alpha mRNA beginning by 6 h postinfection and persisting for up to 7 days postinfection. In addition, exposure of zebrafish to heat-killed bacteria demonstrated that the significant induction of IL-1β was highly specific to live bacteria. Taken together, the pathology and immune response to acute Francisella infection in zebrafish share many features with those in mammals, highlighting the usefulness of this new model system for addressing both general and specific questions about Francisella host-pathogen interactions via an evolutionary approach.

* Corresponding author. Mailing address: USGS—Western Fisheries Research Center, 6505 NE 65th Street, Seattle, WA 98115. Phone: (206) 526-6588. Fax: (206) 526-6654. E-mail: jhansen{at}usgs.gov

{triangledown} Published ahead of print on 1 December 2008.

Editor: A. J. Bäumler

Infection and Immunity, February 2009, p. 914-925, Vol. 77, No. 2
0019-9567/09/$08.00+0     doi:10.1128/IAI.01201-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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