| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Departments of Microbiology, Immunology and Pathology and
Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523
Francisella tularensis is an obligate intracellular bacterium that induces severe, acute, often fatal disease when acquired by the respiratory route. Despite the seriousness of this pathogen, very little is understood about its interaction with key target cells in the airways and lungs (alveolar macrophages and airway dendritic cells (DC)) after inhalation. In this study we demonstrate replication of F. tularensis in primary DC. Early after infection, F. tularensis induced increased expression of MHC class II and CD86 on DC, but not macrophages. This was followed by depletion of DC from the airways and lungs. Despite logarithmic replication and phenotypic maturation of DC, F. tularensis failed to induce production of several key proinflammatory cytokines, including TNF-
and IL-6, from DC. However, F. tularensis infection did elicit production of the potent immunosuppressive cytokine, TGF-
. Furthermore, F. tularensis actively suppressed the ability of DC to secrete cytokines in response to specific TLR agonists. Finally, we also found that infection of DC and macrophages in the lungs appears to actually increase the severity of pulmonary infection with F. tularensis. For example, depletion of airway DC and alveolar macrophages before infection resulted in significantly prolonged survival times. Together, these data suggest F. tularensis is able to selectively uncouple Ag-presenting functions from proinflammatory cytokine secretion by critical APCs in the lungs, which may serve to create a relatively immunosuppressive environment favorable to replication and dissemination of the organism.
This article has been cited by other articles:
|
|
 |
|
  K. England, C. am Ende, H. Lu, T. J. Sullivan, N. L. Marlenee, R. A. Bowen, S. E. Knudson, D. L. Knudson, P. J. Tonge, and R. A. Slayden Substituted diphenyl ethers as a broad-spectrum platform for the development of chemotherapeutics for the treatment of tularaemia J. Antimicrob. Chemother., November 1, 2009; 64(5): 1052 - 1061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. R. Wickstrum, S. M. Bokhari, J. L. Fischer, D. M. Pinson, H.-W. Yeh, R. T. Horvat, and M. J. Parmely Francisella tularensis Induces Extensive Caspase-3 Activation and Apoptotic Cell Death in the Tissues of Infected Mice Infect. Immun., November 1, 2009; 77(11): 4827 - 4836. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sharma, Q. Li, B. B. Mishra, M. J. Georges, and J. M. Teale 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., October 1, 2009; 77(10): 4314 - 4326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. D. Crane, S. L. Warner, and C. M. Bosio A Novel Role for Plasmin-Mediated Degradation of Opsonizing Antibody in the Evasion of Host Immunity by Virulent, but Not Attenuated, Francisella tularensis J. Immunol., October 1, 2009; 183(7): 4593 - 4600. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Cowley Editorial: Proinflammatory cytokines in pneumonic tularemia: too much too late? J. Leukoc. Biol., September 1, 2009; 86(3): 469 - 470. [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Guth, W. J. Janssen, C. M. Bosio, E. C. Crouch, P. M. Henson, and S. W. Dow Lung environment determines unique phenotype of alveolar macrophages Am J Physiol Lung Cell Mol Physiol, June 1, 2009; 296(6): L936 - L946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Collazo, A. I. Meierovics, R. De Pascalis, T. H. Wu, C. R. Lyons, and K. L. Elkins T Cells from Lungs and Livers of Francisella tularensis-Immune Mice Control the Growth of Intracellular Bacteria Infect. Immun., May 1, 2009; 77(5): 2010 - 2021. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Schmerk, B. N. Duplantis, P. L. Howard, and F. E. Nano A Francisella novicida pdpA mutant exhibits limited intracellular replication and remains associated with the lysosomal marker LAMP-1 Microbiology, May 1, 2009; 155(5): 1498 - 1504. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Schmid-Hempel Immune defence, parasite evasion strategies and their relevance for 'macroscopic phenomena' such as virulence Phil Trans R Soc B, January 12, 2009; 364(1513): 85 - 98. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. C. Chase, J. Celli, and C. M. Bosio Direct and Indirect Impairment of Human Dendritic Cell Function by Virulent Francisella tularensis Schu S4 Infect. Immun., January 1, 2009; 77(1): 180 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. D. Hall, M. D. Woolard, B. M. Gunn, R. R. Craven, S. Taft-Benz, J. A. Frelinger, and T. H. Kawula Infected-Host-Cell Repertoire and Cellular Response in the Lung following Inhalation of Francisella tularensis Schu S4, LVS, or U112 Infect. Immun., December 1, 2008; 76(12): 5843 - 5852. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Fuller, R. R. Craven, J. D. Hall, T. M. Kijek, S. Taft-Benz, and T. H. Kawula RipA, a Cytoplasmic Membrane Protein Conserved among Francisella Species, Is Required for Intracellular Survival Infect. Immun., November 1, 2008; 76(11): 4934 - 4943. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Brotcke and D. M. Monack Identification of fevR, a Novel Regulator of Virulence Gene Expression in Francisella novicida Infect. Immun., August 1, 2008; 76(8): 3473 - 3480. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. McGill, N. Van Rooijen, and K. L. Legge Protective influenza-specific CD8 T cell responses require interactions with dendritic cells in the lungs J. Exp. Med., July 7, 2008; 205(7): 1635 - 1646. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Craven, J. D. Hall, J. R. Fuller, S. Taft-Benz, and T. H. Kawula Francisella tularensis Invasion of Lung Epithelial Cells Infect. Immun., July 1, 2008; 76(7): 2833 - 2842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Billard, J. Dornand, and A. Gross Interaction of Brucella suis and Brucella abortus Rough Strains with Human Dendritic Cells Infect. Immun., December 1, 2007; 75(12): 5916 - 5923. [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]
|
|
|
|
|
|
E. Billard, J. Dornand, and A. Gross Brucella suis Prevents Human Dendritic Cell Maturation and Antigen Presentation through Regulation of Tumor Necrosis Factor Alpha Secretion Infect. Immun., October 1, 2007; 75(10): 4980 - 4989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Guina, D. Radulovic, A. J. Bahrami, D. L. Bolton, L. Rohmer, K. A. Jones-Isaac, J. Chen, L. A. Gallagher, B. Gallis, S. Ryu, et al. MglA Regulates Francisella tularensis subsp. novicida (Francisella novicida) Response to Starvation and Oxidative Stress J. Bacteriol., September 15, 2007; 189(18): 6580 - 6586. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Perona-Wright, S. M. Anderton, S. E. M. Howie, and D. Gray IL-10 permits transient activation of dendritic cells to tolerize T cells and protect from central nervous system autoimmune disease Int. Immunol., September 1, 2007; 19(9): 1123 - 1134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
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]
|
|
|
|
|
|
J. D. Hall, R. R. Craven, J. R. Fuller, R. J. Pickles, and T. H. Kawula Francisella tularensis Replicates within Alveolar Type II Epithelial Cells In Vitro and In Vivo following Inhalation Infect. Immun., February 1, 2007; 75(2): 1034 - 1039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. A. Gallagher, E. Ramage, M. A. Jacobs, R. Kaul, M. Brittnacher, and C. Manoil A comprehensive transposon mutant library of Francisella novicida, a bioweapon surrogate PNAS, January 16, 2007; 104(3): 1009 - 1014. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Malik, C. S. Bakshi, K. McCabe, S. V. Catlett, A. Shah, R. Singh, P. L. Jackson, A. Gaggar, D. W. Metzger, J. A. Melendez, et al. Matrix Metalloproteinase 9 Activity Enhances Host Susceptibility to Pulmonary Infection with Type A and B Strains of Francisella tularensis J. Immunol., January 15, 2007; 178(2): 1013 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Ben Nasr, J. Haithcoat, J. E. Masterson, J. S. Gunn, T. Eaves-Pyles, and G. R. Klimpel Critical role for serum opsonins and complement receptors CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in phagocytosis of Francisella tularensis by human dendritic cells (DC): uptake of Francisella leads to activation of immature DC and intracellular survival of the bacteria J. Leukoc. Biol., October 1, 2006; 80(4): 774 - 786. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Katz, P. Zhang, M. Martin, S. N. Vogel, and S. M. Michalek Toll-Like Receptor 2 Is Required for Inflammatory Responses to Francisella tularensis LVS. Infect. Immun., May 1, 2006; 74(5): 2809 - 2816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Jakubzick, F. Tacke, J. Llodra, N. van Rooijen, and G. J. Randolph Modulation of Dendritic Cell Trafficking to and from the Airways J. Immunol., March 15, 2006; 176(6): 3578 - 3584. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
