| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Without Inhibiting STAT1 Function1
* Biomedical Sciences Graduate Program and Division of Infectious Diseases, University of California, San Francisco, CA 94143; and
Departments of Medicine and Microbiology, New York University School of Medicine, New York, NY 10016
Mycobacterium tuberculosis is a highly successful human pathogen. A major component of this success is the pathogen’s ability to avoid eradication by the innate and adaptive immune responses throughout the course of infection. IFN-
, a potent activator of the microbicidal activities of macrophages, is essential for control of M. tuberculosis infection, but is unable to stimulate macrophages to kill M. tuberculosis. We have found that infection of the human monocytic cell line, THP-1, resulted in reduced cellular responses to IFN-, manifested as impaired induction of CD64 surface expression and transcription. This defect in transcription occurred despite normal activation of STAT1 in infected macrophages: there was no decrease in STAT1 tyrosine or serine phosphorylation, nuclear translocation, or binding of a minimal IFN- response sequence. Assays of STAT1 function in M. tuberculosis-treated cells also revealed no defect in activation of a minimal -activated sequence construct or STAT1 recruitment to and binding at the endogenous CD64 promoter. In addition, M. tuberculosis did not affect histone acetylation at the CD64 promoter. The inhibition of transcription was gene selective: while transcription of CD64 and class II transactivator were decreased, certain other IFN--responsive genes either were unaffected or were increased by M. tuberculosis. These results indicate that M. tuberculosis inhibits the response to IFN- by a mechanism distinct from either suppressor of cytokine signaling-1 inhibition of STAT1 phosphorylation or protein inhibitor of activated STAT interference with DNA binding, and indicate that other mechanisms of inhibition of IFN- responses remain to be discovered.
This article has been cited by other articles:
|
|
 |
|
  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]
|
|
|
|
 |
|
 M. E. Pennini, Y. Liu, J. Yang, C. M. Croniger, W. H. Boom, and C. V. Harding CCAAT/Enhancer-Binding Protein beta and {delta} Binding to CIITA Promoters Is Associated with the Inhibition of CIITA Expression in Response to Mycobacterium tuberculosis 19-kDa Lipoprotein J. Immunol., November 15, 2007; 179(10): 6910 - 6918. [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]
|
|
|
|
 |
|
 A. Singhal, A. Jaiswal, V. K. Arora, and H. K. Prasad Modulation of Gamma Interferon Receptor 1 by Mycobacterium tuberculosis: a Potential Immune Response Evasive Mechanism Infect. Immun., May 1, 2007; 75(5): 2500 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. H. Boekhoudt, M. R. Frazier-Jessen, and G. M. Feldman Immune complexes suppress IFN-{gamma} signaling by activation of the Fc{gamma}RI pathway J. Leukoc. Biol., April 1, 2007; 81(4): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. S. Cooke, S. J. Campbell, J. Sillah, P. Gustafson, B. Bah, G. Sirugo, S. Bennett, K. P. W. J. McAdam, O. Sow, C. Lienhardt, et al. Polymorphism within the Interferon-{gamma}/Receptor Complex Is Associated with Pulmonary Tuberculosis Am. J. Respir. Crit. Care Med., August 1, 2006; 174(3): 339 - 343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. D. Pecora, A. J. Gehring, D. H. Canaday, W. H. Boom, and C. V. Harding Mycobacterium tuberculosis LprA Is a Lipoprotein Agonist of TLR2 That Regulates Innate Immunity and APC Function J. Immunol., July 1, 2006; 177(1): 422 - 429. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Pennini, R. K. Pai, D. C. Schultz, W. H. Boom, and C. V. Harding Mycobacterium tuberculosis 19-kDa Lipoprotein Inhibits IFN-{gamma}-Induced Chromatin Remodeling of MHC2TA by TLR2 and MAPK Signaling J. Immunol., April 1, 2006; 176(7): 4323 - 4330. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Jandu, P. J. M. Ceponis, S. Kato, J. D. Riff, D. M. McKay, and P. M. Sherman Conditioned Medium from Enterohemorrhagic Escherichia coli-Infected T84 Cells Inhibits Signal Transducer and Activator of Transcription 1 Activation by Gamma Interferon Infect. Immun., March 1, 2006; 74(3): 1809 - 1818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Banaiee, E. Z. Kincaid, U. Buchwald, W. R. Jacobs Jr., and J. D. Ernst Potent Inhibition of Macrophage Responses to IFN-{gamma} by Live Virulent Mycobacterium tuberculosis Is Independent of Mature Mycobacterial Lipoproteins but Dependent on TLR2. J. Immunol., March 1, 2006; 176(5): 3019 - 3027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Wang, H. M. Curry, B. S. Zwilling, and W. P. Lafuse Mycobacteria Inhibition of IFN-{gamma} Induced HLA-DR Gene Expression by Up-Regulating Histone Deacetylation at the Promoter Region in Human THP-1 Monocytic Cells J. Immunol., May 1, 2005; 174(9): 5687 - 5694. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. T. Chang, J. J. Linderman, and D. E. Kirschner Multiple mechanisms allow Mycobacterium tuberculosis to continuously inhibit MHC class II-mediated antigen presentation by macrophages PNAS, March 22, 2005; 102(12): 4530 - 4535. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Prabhakar, Y. Qiao, A. Canova, D. B. Tse, and R. Pine IFN-{alpha}{beta} Secreted during Infection Is Necessary but Not Sufficient for Negative Feedback Regulation of IFN-{alpha}{beta} Signaling by Mycobacterium tuberculosis J. Immunol., January 15, 2005; 174(2): 1003 - 1012. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Pai, M. E. Pennini, A. A. R. Tobian, D. H. Canaday, W. H. Boom, and C. V. Harding Prolonged Toll-Like Receptor Signaling by Mycobacterium tuberculosis and Its 19-Kilodalton Lipoprotein Inhibits Gamma Interferon-Induced Regulation of Selected Genes in Macrophages Infect. Immun., November 1, 2004; 72(11): 6603 - 6614. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Qing and G. R. Stark Alternative Activation of STAT1 and STAT3 in Response to Interferon-{gamma} J. Biol. Chem., October 1, 2004; 279(40): 41679 - 41685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. J. Gehring, K. M. Dobos, J. T. Belisle, C. V. Harding, and W. H. Boom Mycobacterium tuberculosis LprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing J. Immunol., August 15, 2004; 173(4): 2660 - 2668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Hagge, N. A. Ray, J. L. Krahenbuhl, and L. B. Adams An In Vitro Model for the Lepromatous Leprosy Granuloma: Fate of Mycobacterium leprae from Target Macrophages after Interaction with Normal and Activated Effector Macrophages J. Immunol., June 15, 2004; 172(12): 7771 - 7779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Fortune, A. Solache, A. Jaeger, P. J. Hill, J. T. Belisle, B. R. Bloom, E. J. Rubin, and J. D. Ernst Mycobacterium tuberculosis Inhibits Macrophage Responses to IFN-{gamma} through Myeloid Differentiation Factor 88-Dependent and -Independent Mechanisms J. Immunol., May 15, 2004; 172(10): 6272 - 6280. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Fulton, S. M. Reba, R. K. Pai, M. Pennini, M. Torres, C. V. Harding, and W. H. Boom Inhibition of Major Histocompatibility Complex II Expression and Antigen Processing in Murine Alveolar Macrophages by Mycobacterium bovis BCG and the 19-Kilodalton Mycobacterial Lipoprotein Infect. Immun., April 1, 2004; 72(4): 2101 - 2110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Qiao, S. Prabhakar, A. Canova, Y. Hoshino, M. Weiden, and R. Pine Posttranscriptional Inhibition of Gene Expression by Mycobacterium tuberculosis Offsets Transcriptional Synergism with IFN-{gamma} and Posttranscriptional Up-Regulation by IFN-{gamma} J. Immunol., March 1, 2004; 172(5): 2935 - 2943. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. MacMicking, G. A. Taylor, and J. D. McKinney Immune Control of Tuberculosis by IFN-{gamma}-Inducible LRG-47 Science, October 24, 2003; 302(5645): 654 - 659. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
