| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
CUTTING EDGE |
,2
,,3
* Inflammation Program,
Graduate Program in Immunology, and
Department of Internal Medicine, Division of Infectious Diseases, University of Iowa and Veterans Affairs Medical Center, Iowa City, IA 52242
One-third of the world’s population is infected with Mycobacterium tuberculosis (Mtb), and three million people die of tuberculosis each year. Following its ingestion by macrophages (MPs), Mtb inhibits the maturation of its phagosome, preventing progression to a bactericidal phagolysosome. Phagocytosis of Mtb is uncoupled from the elevation in MP cytosolic Ca2+ that normally accompanies microbial ingestion, resulting in inhibition of phagosome-lysosome fusion and increased intracellular viability. This study demonstrates that the mechanism responsible for this failure of Ca2+-dependent phagosome maturation involves mycobacterial inhibition of MP sphingosine kinase. Thus, inhibition of sphingosine kinase directly contributes to survival of Mtb within human MPs and represents a novel molecular mechanism of pathogenesis.
This article has been cited by other articles:
|
|
 |
|
  S. R Dunn, C. E Schnitzler, and V. M Weis Apoptosis and autophagy as mechanisms of dinoflagellate symbiont release during cnidarian bleaching: every which way you lose Proc R Soc B, December 22, 2007; 274(1629): 3079 - 3085. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Huynh and S. Grinstein Regulation of Vacuolar pH and Its Modulation by Some Microbial Species Microbiol. Mol. Biol. Rev., September 1, 2007; 71(3): 452 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-E. Deghmane, H. Soualhine, H. Bach, K. Sendide, S. Itoh, A. Tam, S. Noubir, A. Talal, R. Lo, S. Toyoshima, et al. Lipoamide dehydrogenase mediates retention of coronin-1 on BCG vacuoles, leading to arrest in phagosome maturation J. Cell Sci., August 15, 2007; 120(16): 2796 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Kusner, C. R. Thompson, N. A. Melrose, S. M. Pitson, L. M. Obeid, and S. S. Iyer The Localization and Activity of Sphingosine Kinase 1 Are Coordinately Regulated with Actin Cytoskeletal Dynamics in Macrophages J. Biol. Chem., August 10, 2007; 282(32): 23147 - 23162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. MacGurn and J. S. Cox A Genetic Screen for Mycobacterium tuberculosis Mutants Defective for Phagosome Maturation Arrest Identifies Components of the ESX-1 Secretion System Infect. Immun., June 1, 2007; 75(6): 2668 - 2678. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. W. Wattenberg, S. M. Pitson, and D. M. Raben The sphingosine and diacylglycerol kinase superfamily of signaling kinases: localization as a key to signaling function J. Lipid Res., June 1, 2006; 47(6): 1128 - 1139. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Yadav, L. Clark, and J. S. Schorey Macrophage's Proinflammatory Response to a Mycobacterial Infection Is Dependent on Sphingosine Kinase-Mediated Activation of Phosphatidylinositol Phospholipase C, Protein Kinase C, ERK1/2, and Phosphatidylinositol 3-Kinase J. Immunol., May 1, 2006; 176(9): 5494 - 5503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Heung, C. Luberto, and M. Del Poeta Role of Sphingolipids in Microbial Pathogenesis Infect. Immun., January 1, 2006; 74(1): 28 - 39. [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Herrmann, C. T. Morita, K. Lee, and D. J. Kusner Calmodulin kinase II regulates the maturation and antigen presentation of human dendritic cells J. Leukoc. Biol., December 1, 2005; 78(6): 1397 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. S. de Felipe, S. Pampou, O. S. Jovanovic, C. D. Pericone, S. F. Ye, S. Kalachikov, and H. A. Shuman Evidence for Acquisition of Legionella Type IV Secretion Substrates via Interdomain Horizontal Gene Transfer J. Bacteriol., November 15, 2005; 187(22): 7716 - 7726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Kang, A. K. Azad, J. B. Torrelles, T. M. Kaufman, A. Beharka, E. Tibesar, L. E. DesJardin, and L. S. Schlesinger The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis J. Exp. Med., October 3, 2005; 202(7): 987 - 999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Thompson, S. S. Iyer, N. Melrose, R. VanOosten, K. Johnson, S. M. Pitson, L. M. Obeid, and D. J. Kusner Sphingosine Kinase 1 (SK1) Is Recruited to Nascent Phagosomes in Human Macrophages: Inhibition of SK1 Translocation by Mycobacterium tuberculosis J. Immunol., March 15, 2005; 174(6): 3551 - 3561. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olivera and J. Rivera Sphingolipids and the Balancing of Immune Cell Function: Lessons from the Mast Cell J. Immunol., February 1, 2005; 174(3): 1153 - 1158. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. V. Vieira, R. E. Harrison, C. C. Scott, H. Stenmark, D. Alexander, J. Liu, J. Gruenberg, A. D. Schreiber, and S. Grinstein Acquisition of Hrs, an Essential Component of Phagosomal Maturation, Is Impaired by Mycobacteria Mol. Cell. Biol., May 15, 2004; 24(10): 4593 - 4604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yadav, S. K. Roach, and J. S. Schorey Increased Mitogen-Activated Protein Kinase Activity and TNF-{alpha} Production Associated with Mycobacterium smegmatis- but Not Mycobacterium avium-Infected Macrophages Requires Prolonged Stimulation of the Calmodulin/Calmodulin Kinase and Cyclic AMP/Protein Kinase A Pathways J. Immunol., May 1, 2004; 172(9): 5588 - 5597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Vergne, J. Chua, and V. Deretic Tuberculosis Toxin Blocking Phagosome Maturation Inhibits a Novel Ca2+/Calmodulin-PI3K hVPS34 Cascade J. Exp. Med., August 18, 2003; 198(4): 653 - 659. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
