Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Originally published in Science Express on 3 August 2006
Science 8 September 2006:
Vol. 313. no. 5792, pp. 1438 - 1441
DOI: 10.1126/science.1129577

Reports

Human IRGM Induces Autophagy to Eliminate Intracellular Mycobacteria

Sudha B. Singh,1 Alexander S. Davis,1 Gregory A. Taylor,3,4 Vojo Deretic1,2*

Immunity-related p47 guanosine triphosphatases (IRG) play a role in defense against intracellular pathogens. We found that the murine Irgm1 (LRG-47) guanosine triphosphatase induced autophagy and generated large autolysosomal organelles as a mechanism for the elimination of intracellular Mycobacterium tuberculosis. We also identified a function for a human IRG protein in the control of intracellular pathogens and report that the human Irgm1 ortholog, IRGM, plays a role in autophagy and in the reduction of intracellular bacillary load.

1 Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
2 Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
3 Department of Medicine, Department of Molecular Genetics and Microbiology, Department of Immunology, Center for the Study of Aging, Duke University, Durham, NC 27710, USA.
4 Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Durham, NC 27710, USA.

* To whom correspondence should be addressed. E-mail: vderetic{at}salud.unm.edu

Read the Full Text



THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Balance of Irgm protein activities determines IFN-{gamma}-induced host defense.
S. C. Henry, X. G. Daniell, A. R. Burroughs, M. Indaram, D. N. Howell, J. Coers, M. N. Starnbach, J. P. Hunn, J. C. Howard, C. G. Feng, et al. (2009)
J. Leukoc. Biol. 85, 877-885
   Abstract »    Full Text »    PDF »
ULK1{middle dot}ATG13{middle dot}FIP200 Complex Mediates mTOR Signaling and Is Essential for Autophagy.
I. G. Ganley, D. H. Lam, J. Wang, X. Ding, S. Chen, and X. Jiang (2009)
J. Biol. Chem. 284, 12297-12305
   Abstract »    Full Text »    PDF »
A Novel Hybrid Yeast-Human Network Analysis Reveals an Essential Role for FNBP1L in Antibacterial Autophagy.
A. Huett, A. Ng, Z. Cao, P. Kuballa, M. Komatsu, M. J. Daly, D. K. Podolsky, and R. J. Xavier (2009)
J. Immunol. 182, 4917-4930
   Abstract »    Full Text »    PDF »
Autophagy Is Essential for Mitochondrial Clearance in Mature T Lymphocytes.
H. H. Pua, J. Guo, M. Komatsu, and Y.-W. He (2009)
J. Immunol. 182, 4046-4055
   Abstract »    Full Text »    PDF »
Autophagy and Its Role in MHC-Mediated Antigen Presentation.
V. L. Crotzer and J. S. Blum (2009)
J. Immunol. 182, 3335-3341
   Abstract »    Full Text »    PDF »
The Gamma Interferon (IFN-{gamma})-Inducible GTP-Binding Protein IGTP Is Necessary for Toxoplasma Vacuolar Disruption and Induces Parasite Egression in IFN-{gamma}-Stimulated Astrocytes.
T. Melzer, A. Duffy, L. M. Weiss, and S. K. Halonen (2008)
Infect. Immun. 76, 4883-4894
   Abstract »    Full Text »    PDF »
Genetics of inflammatory bowel disease: clues to pathogenesis.
H. Zhang, D. Massey, M. Tremelling, and M. Parkes (2008)
Br. Med. Bull. 87, 17-30
   Abstract »    Full Text »    PDF »
Autophagy as an important process in gut homeostasis and Crohn's disease pathogenesis.
R. J Xavier, A. Huett, and J. D Rioux (2008)
Gut 57, 717-720
   Full Text »    PDF »
Chlamydia muridarum Evades Growth Restriction by the IFN-{gamma}-Inducible Host Resistance Factor Irgb10.
J. Coers, I. Bernstein-Hanley, D. Grotsky, I. Parvanova, J. C. Howard, G. A. Taylor, W. F. Dietrich, and M. N. Starnbach (2008)
J. Immunol. 180, 6237-6245
   Abstract »    Full Text »    PDF »
Modulation of the Phagosome Proteome by Interferon-{gamma}.
I. Jutras, M. Houde, N. Currier, J. Boulais, S. Duclos, S. LaBoissiere, E. Bonneil, P. Kearney, P. Thibault, E. Paramithiotis, et al. (2008)
Mol. Cell. Proteomics 7, 697-715
   Abstract »    Full Text »    PDF »
Autophagy: process and function.
N. Mizushima (2007)
Genes & Dev. 21, 2861-2873
   Abstract »    Full Text »    PDF »
Impaired Macrophage Function Underscores Susceptibility to Salmonella in Mice Lacking Irgm1 (LRG-47).
S. C. Henry, X. Daniell, M. Indaram, J. F. Whitesides, G. D. Sempowski, D. Howell, T. Oliver, and G. A. Taylor (2007)
J. Immunol. 179, 6963-6972
   Abstract »    Full Text »    PDF »
Common pathways in Crohn's disease and other inflammatory diseases revealed by genomics.
D. Massey and M. Parkes (2007)
Gut 56, 1489-1492
   Abstract »    Full Text »    PDF »
The IFN-Inducible GTPase LRG47 (Irgm1) Negatively Regulates TLR4-Triggered Proinflammatory Cytokine Production and Prevents Endotoxemia.
A. Bafica, C. G. Feng, H. C. Santiago, J. Aliberti, A. Cheever, K. E. Thomas, G. A. Taylor, S. N. Vogel, and A. Sher (2007)
J. Immunol. 179, 5514-5522
   Abstract »    Full Text »    PDF »
The p47 GTPases Iigp2 and Irgb10 Regulate Innate Immunity and Inflammation to Murine Chlamydia psittaci Infection.
I. Miyairi, V. R. R. A. Tatireddigari, O. S. Mahdi, L. A. Rose, R. J. Belland, L. Lu, R. W. Williams, and G. I. Byrne (2007)
J. Immunol. 179, 1814-1824
   Abstract »    Full Text »    PDF »
IL-1 Receptor-Mediated Signal Is an Essential Component of MyD88-Dependent Innate Response to Mycobacterium tuberculosis Infection.
C. M. Fremond, D. Togbe, E. Doz, S. Rose, V. Vasseur, I. Maillet, M. Jacobs, B. Ryffel, and V. F. J. Quesniaux (2007)
J. Immunol. 179, 1178-1189
   Abstract »    Full Text »    PDF »
Autophagy: Eating for Good Health.
M. S. Swanson (2006)
J. Immunol. 177, 4945-4951
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)