| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
by Live Virulent Mycobacterium tuberculosis Is Independent of Mature Mycobacterial Lipoproteins but Dependent on TLR21
,
* Department of Medicine, Division of Infectious Diseases, New York University School of Medicine, New York, NY 10016;
Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143;
Howard Hughes Medical Institute and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461; and
Department of Microbiology, New York University School of Medicine, New York, NY 10016
Mycobacterium tuberculosis is a highly successful pathogen that can persist and cause disease despite an immune response. One potential mechanism for resisting elimination is by inhibiting the action of IFN-
. We have previously shown that live M. tuberculosis inhibits selected macrophage responses to IFN-, and that purified M. tuberculosis 19-kDa lipoprotein inhibits induction of selected IFN--responsive genes through a TLR2-dependent pathway, whereas peptidoglycan inhibits responses to IFN- by a TLR2-independent pathway. To determine the relative contribution of lipoproteins to the inhibition of responses to IFN-, we deleted the M. tuberculosis gene (lspA) that encodes lipoprotein signal peptidase. This revealed that M. tuberculosis lipoprotein processing is indispensable for stimulation of TLR2 reporter cells, but that the lspA mutant inhibits macrophage responses to IFN- to the same extent as wild-type bacteria. Macrophages lacking TLR2 are more resistant to inhibition by either strain of M. tuberculosis, suggesting that nonlipoprotein TLR2 agonists contribute to inhibition. Indeed, we found that phosphatidylinositol mannan from M. tuberculosis inhibits macrophage responses to IFN-. M. tuberculosis inhibition of responses to IFN- requires new protein synthesis, indicating that a late effect of innate immune stimulation is the inhibition of responses to IFN-. These results establish that M. tuberculosis possesses multiple mechanisms of inhibiting responses to IFN-.
This article has been cited by other articles:
|
|
 |
|
  N. Banaei, E. Z. Kincaid, S.-Y. G. Lin, E. Desmond, W. R. Jacobs Jr., and J. D. Ernst Lipoprotein Processing Is Essential for Resistance of Mycobacterium tuberculosis to Malachite Green Antimicrob. Agents Chemother., September 1, 2009; 53(9): 3799 - 3802. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. G. Rothfuchs, J. G. Egen, C. G. Feng, L. R. V. Antonelli, A. Bafica, N. Winter, R. M. Locksley, and A. Sher In Situ IL-12/23p40 Production during Mycobacterial Infection Is Sustained by CD11bhigh Dendritic Cells Localized in Tissue Sites Distinct from Those Harboring Bacilli J. Immunol., June 1, 2009; 182(11): 6915 - 6925. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bansal, Y. Narayana, S. A. Patil, and K. N. Balaji M. bovis BCG induced expression of COX-2 involves nitric oxide-dependent and -independent signaling pathways J. Leukoc. Biol., May 1, 2009; 85(5): 804 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Jeyanathan, J. Mu, K. Kugathasan, X. Zhang, D. Damjanovic, C. Small, M. Divangahi, B. J. Petrof, C. M. Hogaboam, and Z. Xing Airway Delivery of Soluble Mycobacterial Antigens Restores Protective Mucosal Immunity by Single Intramuscular Plasmid DNA Tuberculosis Vaccination: Role of Proinflammatory Signals in the Lung J. Immunol., October 15, 2008; 181(8): 5618 - 5626. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. K. Rampini, P. Selchow, C. Keller, S. Ehlers, E. C. Bottger, and P. Sander LspA inactivation in Mycobacterium tuberculosis results in attenuation without affecting phagosome maturation arrest Microbiology, October 1, 2008; 154(10): 2991 - 3001. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Narayana and K. N. Balaji NOTCH1 Up-regulation and Signaling Involved in Mycobacterium bovis BCG-induced SOCS3 Expression in Macrophages J. Biol. Chem., May 2, 2008; 283(18): 12501 - 12511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. A. Sieling, P. J. Hill, K. M. Dobos, K. Brookman, A. M. Kuhlman, M. Fabri, S. R. Krutzik, T. H. Rea, D. G. Heaslip, J. T. Belisle, et al. Conserved Mycobacterial Lipoglycoproteins Activate TLR2 but Also Require Glycosylation for MHC Class II-Restricted T Cell Activation J. Immunol., May 1, 2008; 180(9): 5833 - 5842. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bastian, T. Braun, H. Bruns, M. Rollinghoff, and S. Stenger Mycobacterial Lipopeptides Elicit CD4+ CTLs in Mycobacterium tuberculosis-Infected Humans J. Immunol., March 1, 2008; 180(5): 3436 - 3446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. Wolf, L. Desvignes, B. Linas, N. Banaiee, T. Tamura, K. Takatsu, and J. D. Ernst Initiation of the adaptive immune response to Mycobacterium tuberculosis depends on antigen production in the local lymph node, not the lungs J. Exp. Med., January 21, 2008; 205(1): 105 - 115. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Weiss, C. D. Souza, O. A. Evanson, M. Sanders, and M. Rutherford Bovine monocyte TLR2 receptors differentially regulate the intracellular fate of Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium J. Leukoc. Biol., January 1, 2008; 83(1): 48 - 55. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Z. Kincaid, A. J. Wolf, L. Desvignes, S. Mahapatra, D. C. Crick, P. J. Brennan, M. S. Pavelka Jr., and J. D. Ernst Codominance of TLR2-Dependent and TLR2-Independent Modulation of MHC Class II in Mycobacterium tuberculosis Infection In Vivo J. Immunol., September 1, 2007; 179(5): 3187 - 3195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Banaiee, W. R. Jacobs, and J. D. Ernst LspA-independent action of globomycin on Mycobacterium tuberculosis J. Antimicrob. Chemother., August 1, 2007; 60(2): 414 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. S. Gibbons, F. Wolschendorf, M. Abshire, M. Niederweis, and M. Braunstein Identification of Two Mycobacterium smegmatis Lipoproteins Exported by a SecA2-Dependent Pathway J. Bacteriol., July 15, 2007; 189(14): 5090 - 5100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Johnson, E. A. Lyle, K. O. Omueti, V. A. Stepensky, O. Yegin, E. Alpsoy, L. Hamann, R. R. Schumann, and R. I. Tapping Cutting Edge: A Common Polymorphism Impairs Cell Surface Trafficking and Functional Responses of TLR1 but Protects against Leprosy J. Immunol., June 15, 2007; 178(12): 7520 - 7524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. W. Yew and C. C. Leung Update in Tuberculosis 2006 Am. J. Respir. Crit. Care Med., March 15, 2007; 175(6): 541 - 546. [Full Text] [PDF]
|
|
|
|
|
|
M. Rezwan, T. Grau, A. Tschumi, and P. Sander Lipoprotein synthesis in mycobacteria Microbiology, March 1, 2007; 153(3): 652 - 658. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
