Journal of Leukocyte Biology BioLegend: Treg, Th17, Stem Cell
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on December 1, 2006

Published online before print August 14, 2006
This Article
Right arrow Full Text (Reprint (PDF))
Right arrow All Versions of this Article:
jlb.0406287v1
80/6/1224    most recent
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by McCaffrey, R. L.
Right arrow Articles by Allen*, L.-A. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by McCaffrey, R. L.
Right arrow Articles by Allen*, L.-A. H.
Related Collections
Right arrowRelated Article
© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0406287

Received for publication April 21, 2006.

Accepted for publication May 17, 2006.

Article

Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape

Ramona L. McCaffrey *{dagger} and Lee-Ann H. Allen* *{dagger}{ddagger}@

*Inflammation Program and Departments of {dagger}Medicine and {ddagger}Microbiology, University of Iowa and the VA Medical Center, Iowa City

@ To whom correspondence should be addressed. E-mail: lee-ann-allen{at}uiowa.edu.


  Abstract

Francisella tularensis is a Gram-negative bacterium and the causative agent of tularemia. Recent data indicate that F. tularensis replicates inside macrophages, but its fate in other cell types, including human neutrophils, is unclear. We now show that F. tularensis live vaccine strain (LVS), opsonized with normal human serum, was rapidly ingested by neutrophils but was not eliminated. Moreover, evasion of intracellular killing can be explained, in part, by disruption of the respiratory burst. As judged by luminol-enhanced chemiluminescence and nitroblue tetrazolium staining, neutrophils infected with live F. tularensis did not generate reactive oxygen species. Confocal microscopy demonstrated that NADPH oxidase assembly was disrupted, and LVS phagosomes did not acquire gp91/p22phox or p47/p67phox. At the same time, F. tularensis also impaired neutrophil activation by heterologous stimuli such as phorbol esters and opsonized zymosan particles. Later in infection, LVS escaped the phagosome, and live organisms persisted in the neutrophil cytosol for at least 12 h. To our knowledge, our data are the first demonstration of a facultative intracellular pathogen, which disrupts the oxidative burst and escapes the phagosome to evade elimination inside neutrophils, and as such, our data define a novel mechanism of virulence.

Key Words: NADPH oxidase • tularemia • superoxide


Related Article

Interview with Dr. Lee-Ann Allen regarding Pivotal Advance: Francisella tularensis LVS evades killing by human neutrophils via inhibition of the respiratory burst and phagosome escape
Helene F. Rosenberg
J. Leukoc. Biol. 2006 80: 1222-1223. [Full Text] [PDF]



This article has been cited by other articles:


Home page
 J Med MicrobiolHome page
P. C. F. Oyston
Francisella tularensis: unravelling the secrets of an intracellular pathogen
J. Med. Microbiol., August 1, 2008; 57(8): 921 - 930.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
C. A. Mares, S. S. Ojeda, E. G. Morris, Q. Li, and J. M. Teale
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., July 1, 2008; 76(7): 3001 - 3010.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
M. D. Woolard, L. L. Hensley, T. H. Kawula, and J. A. Frelinger
Respiratory Francisella tularensis Live Vaccine Strain Infection Induces Th17 Cells and Prostaglandin E2, Which Inhibits Generation of Gamma Interferon-Positive T Cells
Infect. Immun., June 1, 2008; 76(6): 2651 - 2659.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Lembo, M. Pelletier, R. Iyer, M. Timko, J. C. Dudda, T. E. West, C. B. Wilson, A. M. Hajjar, and S. J. Skerrett
Administration of a Synthetic TLR4 Agonist Protects Mice from Pneumonic Tularemia
J. Immunol., June 1, 2008; 180(11): 7574 - 7581.
[Abstract] [Full Text] [PDF]

Home page
 Appl. Environ. Microbiol.Home page
B. W. Buchan, M. K. McLendon, and B. D. Jones
Identification of Differentially Regulated Francisella tularensis Genes by Use of a Newly Developed Tn5-Based Transposon Delivery System
Appl. Envir. Microbiol., May 1, 2008; 74(9): 2637 - 2645.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. R. Lindemann, M. K. McLendon, M. A. Apicella, and B. D. Jones
An In Vitro Model System Used To Study Adherence and Invasion of Francisella tularensis Live Vaccine Strain in Nonphagocytic Cells
Infect. Immun., June 1, 2007; 75(6): 3178 - 3182.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
D. S. Weiss, A. Brotcke, T. Henry, J. J. Margolis, K. Chan, and D. M. Monack
In vivo negative selection screen identifies genes required for Francisella virulence
PNAS, April 3, 2007; 104(14): 6037 - 6042.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
H. Lindgren, H. Shen, C. Zingmark, I. Golovliov, W. Conlan, and A. Sjostedt
Resistance of Francisella tularensis Strains against Reactive Nitrogen and Oxygen Species with Special Reference to the Role of KatG
Infect. Immun., March 1, 2007; 75(3): 1303 - 1309.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by the Society for Leukocyte Biology.