| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1
* Division of Infectious Diseases, University of California, and Loewenstein Laboratory for Tuberculosis Research, San Francisco General Hospital, San Francisco, CA 94110;
Trudeau Institute, Saranac Lake, NY 12983;
Department of Medicine and Microbiology and Immunology, Albert Einstein College of Medicine, New York, NY 10461;
Department of Dermatology, Stanford University, Stanford, CA 94305; and
¶
Departments of Medicine and Microbiology, New York University School of Medicine, New York, NY 10016
In humans and in mice, control of the intracellular pathogen, Mycobacterium tuberculosis (Mtb), requires IFN-
. Although the adaptive immune response results in production of substantial amounts of IFN- in response to Mtb, the immune response is unable to eradicate the infection in most cases. We have previously reported evidence that Mtb inhibits macrophage responses to IFN-, suggesting that this may limit the ability of IFN- to stimulate macrophages to kill Mtb. We have also observed that uninfected macrophages, adjacent to infected macrophages in culture, exhibit decreased responses to IFN-. Here we report that IL-6 secreted by Mtb-infected macrophages inhibits the responses of uninfected macrophages to IFN-. IL-6 selectively inhibits a subset of IFN--responsive genes at the level of transcriptional activation without inhibiting activation or function of STAT1. Inhibition of macrophage responses to IFN- by IL-6 requires new protein synthesis, but this effect is not attributable to suppressor of cytokine signaling 1 or 3. These results reveal a novel function for IL-6 and indicate that IL-6 secreted by Mtb-infected macrophages may contribute to the inability of the cellular immune response to eradicate infection.
This article has been cited by other articles:
|
|
 |
|
  J. E. Wilson, B. Katkere, and J. R. Drake Francisella tularensis Induces Ubiquitin-Dependent Major Histocompatibility Complex Class II Degradation in Activated Macrophages Infect. Immun., November 1, 2009; 77(11): 4953 - 4965. [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. Benoit, B. Desnues, and J.-L. Mege Macrophage Polarization in Bacterial Infections J. Immunol., September 15, 2008; 181(6): 3733 - 3739. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. W. Murray Accelerated Control of Visceral Leishmania donovani Infection in Interleukin-6-Deficient Mice Infect. Immun., September 1, 2008; 76(9): 4088 - 4091. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Welsh, A. N. Abbott, S.-A. Hwang, J. Indrigo, L. Y. Armitige, M. R. Blackburn, R. L. Hunter, and J. K. Actor A role for tumour necrosis factor-{alpha}, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6'-dimycolate induced granulomatous response Microbiology, June 1, 2008; 154(6): 1813 - 1824. [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. Barrionuevo, J. Cassataro, M. V. Delpino, A. Zwerdling, K. A. Pasquevich, C. G. Samartino, J. C. Wallach, C. A. Fossati, and G. H. Giambartolomei Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2 Infect. Immun., January 1, 2008; 76(1): 250 - 262. [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]
|
|
|
|
 |
|
 L. H. Hogan, E. Heninger, R. A. Elsner, H. A. Vonderheid, P. Hulseberg, D. Co, and M. Sandor Requirements for CD4+ T cell levels in acute Mycobacterium bovis strain bacille Calmette Guerin (BCG)-induced granulomas differ for optimal mycobacterial control versus granuloma formation Int. Immunol., May 1, 2007; 19(5): 627 - 633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Humann, R. Bjordahl, K. Andreasen, and L. L. Lenz Expression of the p60 Autolysin Enhances NK Cell Activation and Is Required for Listeria monocytogenes Expansion in IFN-{gamma}-Responsive Mice J. Immunol., February 15, 2007; 178(4): 2407 - 2414. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kurtz, K. P. McKinnon, M. S. Runge, J. P.-Y. Ting, and M. Braunstein The SecA2 Secretion Factor of Mycobacterium tuberculosis Promotes Growth in Macrophages and Inhibits the Host Immune Response Infect. Immun., December 1, 2006; 74(12): 6855 - 6864. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. A. Rowland, G. Lertmemongkolchai, A. Bancroft, A. Haque, M. S. Lever, K. F. Griffin, M. C. Jackson, M. Nelson, A. O'Garra, R. Grencis, et al. Critical Role of Type 1 Cytokines in Controlling Initial Infection with Burkholderia mallei Infect. Immun., September 1, 2006; 74(9): 5333 - 5340. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. O. Orlova, K. B. Majorov, I. V. Lyadova, E. B. Eruslanov, C. E. M'lan, C. M. T. Greenwood, E. Schurr, and A. S. Apt Constitutive differences in gene expression profiles parallel genetic patterns of susceptibility to tuberculosis in mice. Infect. Immun., June 1, 2006; 74(6): 3668 - 3672. [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]
|
|
|
|
|
|
R. E. Geisel, K. Sakamoto, D. G. Russell, and E. R. Rhoades In Vivo Activity of Released Cell Wall Lipids of Mycobacterium bovis Bacillus Calmette-Guerin Is Due Principally to Trehalose Mycolates J. Immunol., April 15, 2005; 174(8): 5007 - 5015. [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]
|
|
|
|
|
|
K. B. Hisert, M. A. Kirksey, J. E. Gomez, A. O. Sousa, J. S. Cox, W. R. Jacobs Jr., C. F. Nathan, and J. D. McKinney Identification of Mycobacterium tuberculosis Counterimmune (cim) Mutants in Immunodeficient Mice by Differential Screening Infect. Immun., September 1, 2004; 72(9): 5315 - 5321. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Jang, S. Uematsu, S. Akira, and P. Salgame IL-6 and IL-10 Induction from Dendritic Cells in Response to Mycobacterium tuberculosis Is Predominantly Dependent on TLR2-Mediated Recognition J. Immunol., September 1, 2004; 173(5): 3392 - 3397. [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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
