Published online before print August 8, 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department Molecular Sciences, University of Tennessee Health Science Center, Memphis, Tennessee
1 Correspondence: Department Molecular Sciences, University of Tennessee Health Science Center, 858 Madison Avenue, MSB 501B, Memphis, TN 38163. E-mail: fre{at}utmem.edu
ABSTRACT
Francisella tularensis, a gram-negative, facultative, intracellular bacterium, is the etiologic agent of tularemia and a category A bioterrorism agent. Little is known about the mechanism of pathogenesis of tularemia. In this paper, we describe the interaction of the live vaccine strain of F. tularensis with the innate immune system. We have found that in human and mouse dendritic cells, F. tularensis elicited a powerful inflammatory response, characterized by production of a number of cytokines and chemokines. Using cells derived from TLR2-deficient mice and in vitro transfection assays, we demonstrated that this response was mediated by TLR2 and did not require the LPS-binding protein. F. tularensis appeared to activate TLR2/TLR1 and TLR2/TLR6 heterodimers. IL-1ß secretion, a reflection of caspase-1 activation, was induced by live but not heat-killed F. tularensis, despite the fact that both forms of the bacterium equally induced the IL-1ß transcript. Our results identified activation of TLR2 and caspase-1 as the two main cellular pathways responsible for the inflammatory response to F. tularensis.
Key Words: Toll-like receptors • inflammation • dendritic cells • bacterial infection
This article has been cited by other articles:
 |
|
 |
|
  G. S. Schulert, R. L. McCaffrey, B. W. Buchan, S. R. Lindemann, C. Hollenback, B. D. Jones, and L.-A. H. Allen Francisella tularensis Genes Required for Inhibition of the Neutrophil Respiratory Burst and Intramacrophage Growth Identified by Random Transposon Mutagenesis of Strain LVS Infect. Immun., April 1, 2009; 77(4): 1324 - 1336. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. N. Vojtech, G. E. Sanders, C. Conway, V. Ostland, and J. D. Hansen Host Immune Response and Acute Disease in a Zebrafish Model of Francisella Pathogenesis Infect. Immun., February 1, 2009; 77(2): 914 - 925. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Qin, D. W. Scott, J. A. Thompson, and B. J. Mann Identification of an Essential Francisella tularensis subsp. tularensis Virulence Factor Infect. Immun., January 1, 2009; 77(1): 152 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Ashtekar, P. Zhang, J. Katz, C. C. S. Deivanayagam, P. Rallabhandi, S. N. Vogel, and S. M. Michalek TLR4-mediated activation of dendritic cells by the heat shock protein DnaK from Francisella tularensis J. Leukoc. Biol., December 1, 2008; 84(6): 1434 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Thakran, H. Li, C. L. Lavine, M. A. Miller, J. E. Bina, X. R. Bina, and F. Re Identification of Francisella tularensis Lipoproteins That Stimulate the Toll-like Receptor (TLR) 2/TLR1 Heterodimer J. Biol. Chem., February 15, 2008; 283(7): 3751 - 3760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Li, M. M. Nooh, M. Kotb, and F. Re Commercial peptidoglycan preparations are contaminated with superantigen-like activity that stimulates IL-17 production J. Leukoc. Biol., February 1, 2008; 83(2): 409 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K.-J. Hong, J. R. Wickstrum, H.-W. Yeh, and M. J. Parmely Toll-Like Receptor 2 Controls the Gamma Interferon Response to Francisella tularensis by Mouse Liver Lymphocytes Infect. Immun., November 1, 2007; 75(11): 5338 - 5345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Gentry, J. Taormina, R. B. Pyles, L. Yeager, M. Kirtley, V. L. Popov, G. Klimpel, and T. Eaves-Pyles Role of Primary Human Alveolar Epithelial Cells in Host Defense against Francisella tularensis Infection Infect. Immun., August 1, 2007; 75(8): 3969 - 3978. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Li, S. Nookala, and F. Re Aluminum Hydroxide Adjuvants Activate Caspase-1 and Induce IL-1beta and IL-18 Release J. Immunol., April 15, 2007; 178(8): 5271 - 5276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Bosio, H. Bielefeldt-Ohmann, and J. T. Belisle Active Suppression of the Pulmonary Immune Response by Francisella tularensis Schu4 J. Immunol., April 1, 2007; 178(7): 4538 - 4547. [Abstract] [Full Text] [PDF]
|
|
