This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chan, J Articles by Bloom, B R Search for Related Content PubMed PubMed Citation Articles by Chan, J Articles by Bloom, B R

 Previous Article  |  Next Article 

Infect Immun. 1991 May; 59(5): 1755-1761

Lipoarabinomannan, a possible virulence factor involved in persistence of Mycobacterium tuberculosis within macrophages.

Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark 07103.

ABSTRACT

Mycobacterium tuberculosis and Mycobacterium leprae, the causative agents of tuberculosis and leprosy, respectively, produce large quantities of lipoarabinomannan (LAM), a highly immunogenic, cell wall-associated glycolipid. This molecule has been previously reported to be a potent inhibitor of gamma interferon-mediated activation of murine macrophages. Studies of the mechanism by which this mycobacterial glycolipid down-regulates macrophage effector functions provide evidence that LAM acts at several levels and that it can (i) scavenge potentially cytotoxic oxygen free radicals, (ii) inhibit protein kinase C activity, and (iii) block the transcriptional activation of gamma interferon-inducible genes in human macrophage-like cell lines. These results suggest that LAM can inhibit macrophage activation and triggering and cytocidal activity and that it may represent a chemically defined virulence factor contributing to the persistence of mycobacteria within mononuclear phagocytes.

This article has been cited by other articles:

• Ito, T., Hasegawa, A., Hosokawa, H., Yamashita, M., Motohashi, S., Naka, T., Okamoto, Y., Fujita, Y., Ishii, Y., Taniguchi, M., Yano, I., Nakayama, T. (2008). Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172. Int Immunol 20: 849-860 [Abstract] [Full Text]  
• Goude, R., Amin, A. G., Chatterjee, D., Parish, T. (2008). The Critical Role of embC in Mycobacterium tuberculosis. J. Bacteriol. 190: 4335-4341 [Abstract] [Full Text]  
• Mizusawa, M., Kawamura, M., Takamori, M., Kashiyama, T., Fujita, A., Usuzawa, M., Saitoh, H., Ashino, Y., Yano, I., Hattori, T. (2008). Increased Synthesis of Anti-Tuberculous Glycolipid Immunoglobulin G (IgG) and IgA with Cavity Formation in Patients with Pulmonary Tuberculosis. CVI 15: 544-548 [Abstract] [Full Text]  
• Samuel, L. P., Song, C.-H., Wei, J., Roberts, E. A., Dahl, J. L., Barry, C. E. III, Jo, E.-K., Friedman, R. L. (2007). Expression, production and release of the Eis protein by Mycobacterium tuberculosis during infection of macrophages and its effect on cytokine secretion. Microbiology 153: 529-540 [Abstract] [Full Text]  
• Sahiratmadja, E., Alisjahbana, B., de Boer, T., Adnan, I., Maya, A., Danusantoso, H., Nelwan, R. H. H., Marzuki, S., van der Meer, J. W. M., van Crevel, R., van de Vosse, E., Ottenhoff, T. H. M. (2007). Dynamic Changes in Pro- and Anti-Inflammatory Cytokine Profiles and Gamma Interferon Receptor Signaling Integrity Correlate with Tuberculosis Disease Activity and Response to Curative Treatment. Infect. Immun. 75: 820-829 [Abstract] [Full Text]  
• Zajonc, D. M., Ainge, G. D., Painter, G. F., Severn, W. B., Wilson, I. A. (2006). Structural Characterization of Mycobacterial Phosphatidylinositol Mannoside Binding to Mouse CD1d. J. Immunol. 177: 4577-4583 [Abstract] [Full Text]  
• Daniel, D. S., Dai, G., Singh, C. R., Lindsey, D. R., Smith, A. K., Dhandayuthapani, S., Hunter, R. L. Jr, Jagannath, C. (2006). The Reduced Bactericidal Function of Complement C5-Deficient Murine Macrophages Is Associated with Defects in the Synthesis and Delivery of Reactive Oxygen Radicals to Mycobacterial Phagosomes. J. Immunol. 177: 4688-4698 [Abstract] [Full Text]  
• Warner, D. F., Mizrahi, V. (2006). Tuberculosis Chemotherapy: the Influence of Bacillary Stress and Damage Response Pathways on Drug Efficacy. Clin. Microbiol. Rev. 19: 558-570 [Abstract] [Full Text]  
• Chang, W., Small, D. A., Toghrol, F., Bentley, W. E. (2006). Global Transcriptome Analysis of Staphylococcus aureus Response to Hydrogen Peroxide. J. Bacteriol. 188: 1648-1659 [Abstract] [Full Text]  
• Berg, S., Starbuck, J., Torrelles, J. B., Vissa, V. D., Crick, D. C., Chatterjee, D., Brennan, P. J. (2005). Roles of Conserved Proline and Glycosyltransferase Motifs of EmbC in Biosynthesis of Lipoarabinomannan. J. Biol. Chem. 280: 5651-5663 [Abstract] [Full Text]  
• Fortune, S. M., Solache, A., Jaeger, A., Hill, P. J., Belisle, J. T., Bloom, B. R., Rubin, E. J., Ernst, J. D. (2004). Mycobacterium tuberculosis Inhibits Macrophage Responses to IFN-{gamma} through Myeloid Differentiation Factor 88-Dependent and -Independent Mechanisms. J. Immunol. 172: 6272-6280 [Abstract] [Full Text]  
• Nagabhushanam, V., Solache, A., Ting, L.-M., Escaron, C. J., Zhang, J. Y., Ernst, J. D. (2003). Innate Inhibition of Adaptive Immunity: Mycobacterium tuberculosis-Induced IL-6 Inhibits Macrophage Responses to IFN-{gamma}. J. Immunol. 171: 4750-4757 [Abstract] [Full Text]  
• Gibson, K. J. C., Eggeling, L., Maughan, W. N., Krumbach, K., Gurcha, S. S., Nigou, J., Puzo, G., Sahm, H., Besra, G. S. (2003). Disruption of Cg-Ppm1, a Polyprenyl Monophosphomannose Synthase, and the Generation of Lipoglycan-less Mutants in Corynebacterium glutamicum. J. Biol. Chem. 278: 40842-40850 [Abstract] [Full Text]  
• Hestvik, A. L. K., Hmama, Z., Av-Gay, Y. (2003). Kinome Analysis of Host Response to Mycobacterial Infection: a Novel Technique in Proteomics. Infect. Immun. 71: 5514-5522 [Abstract] [Full Text]  
• Guerardel, Y., Maes, E., Briken, V., Chirat, F., Leroy, Y., Locht, C., Strecker, G., Kremer, L. (2003). Lipomannan and Lipoarabinomannan from a Clinical Isolate of Mycobacterium kansasii: NOVEL STRUCTURAL FEATURES AND APOPTOSIS-INDUCING PROPERTIES. J. Biol. Chem. 278: 36637-36651 [Abstract] [Full Text]  
• Kincaid, E. Z., Ernst, J. D. (2003). Mycobacterium tuberculosis Exerts Gene-Selective Inhibition of Transcriptional Responses to IFN-{gamma} Without Inhibiting STAT1 Function. J. Immunol. 171: 2042-2049 [Abstract] [Full Text]  
• Smith, I. (2003). Mycobacterium tuberculosis Pathogenesis and Molecular Determinants of Virulence. Clin. Microbiol. Rev. 16: 463-496 [Abstract] [Full Text]  
• Prabhakar, S., Qiao, Y., Hoshino, Y., Weiden, M., Canova, A., Giacomini, E., Coccia, E., Pine, R. (2003). Inhibition of Response to Alpha Interferon by Mycobacterium tuberculosis. Infect. Immun. 71: 2487-2497 [Abstract] [Full Text]  
• Sirkar, M., Majumdar, S. (2002). Lipoarabinomannan-Induced Cell Signaling Involves Ceramide and Mitogen-Activated Protein Kinase. CVI 9: 1175-1182 [Abstract] [Full Text]  
• Ludwiczak, P., Gilleron, M., Bordat, Y., Martin, C., Gicquel, B., Puzo, G. (2002). Mycobacterium tuberculosis phoP mutant: lipoarabinomannan molecular structure. Microbiology 148: 3029-3037 [Abstract] [Full Text]  
• Guerardel, Y., Maes, E., Elass, E., Leroy, Y., Timmerman, P., Besra, G. S., Locht, C., Strecker, G., Kremer, L. (2002). Structural Study of Lipomannan and Lipoarabinomannan from Mycobacterium chelonae. PRESENCE OF UNUSUAL COMPONENTS WITH alpha 1,3-MANNOPYRANOSE SIDE CHAINS. J. Biol. Chem. 277: 30635-30648 [Abstract] [Full Text]  
• van Crevel, R., Ottenhoff, T. H. M., van der Meer, J. W. M. (2002). Innate Immunity to Mycobacterium tuberculosis. Clin. Microbiol. Rev. 15: 294-309 [Abstract] [Full Text]  
• Peteroy-Kelly, M., Venketaraman, V., Connell, N. D. (2001). Effects of Mycobacterium bovis BCG Infection on Regulation of L-Arginine Uptake and Synthesis of Reactive Nitrogen Intermediates in J774.1 Murine Macrophages. Infect. Immun. 69: 5823-5831 [Abstract] [Full Text]  
• Fischer, K., Chatterjee, D., Torrelles, J., Brennan, P. J., Kaufmann, S. H. E., Schaible, U. E. (2001). Mycobacterial Lysocardiolipin Is Exported from Phagosomes upon Cleavage of Cardiolipin by a Macrophage-Derived Lysosomal Phospholipase A2. J. Immunol. 167: 2187-2192 [Abstract] [Full Text]  
• Piddington, D. L., Fang, F. C., Laessig, T., Cooper, A. M., Orme, I. M., Buchmeier, N. A. (2001). Cu,Zn Superoxide Dismutase of Mycobacterium tuberculosis Contributes to Survival in Activated Macrophages That Are Generating an Oxidative Burst. Infect. Immun. 69: 4980-4987 [Abstract] [Full Text]  
• Dahl, J. L., Wei, J., Moulder, J. W., Laal, S., Friedman, R. L. (2001). Subcellular Localization of the Intracellular Survival-Enhancing Eis Protein of Mycobacterium tuberculosis. Infect. Immun. 69: 4295-4302 [Abstract] [Full Text]  
• Master, S., Zahrt, T. C., Song, J., Deretic, V. (2001). Mapping of Mycobacterium tuberculosis katG Promoters and Their Differential Expression in Infected Macrophages. J. Bacteriol. 183: 4033-4039 [Abstract] [Full Text]  
• Chan, E. D., Morris, K. R., Belisle, J. T., Hill, P., Remigio, L. K., Brennan, P. J., Riches, D. W. H. (2001). Induction of Inducible Nitric Oxide Synthase-NO{middle dot} by Lipoarabinomannan of Mycobacterium tuberculosis Is Mediated by MEK1-ERK, MKK7-JNK, and NF-{kappa}B Signaling Pathways. Infect. Immun. 69: 2001-2010 [Abstract] [Full Text]  
• Thorson, L. M., Doxsee, D., Scott, M. G., Wheeler, P., Stokes, R. W. (2001). Effect of Mycobacterial Phospholipids on Interaction of Mycobacterium tuberculosis with Macrophages. Infect. Immun. 69: 2172-2179 [Abstract] [Full Text]  
• Rook, G.A.W., Seah, G., Ustianowski, A. (2001). M. tuberculosis: immunology and vaccination. Eur Respir J 17: 537-557 [Abstract] [Full Text]  
• Koets, A. P., Rutten, V. P. M. G., de Boer, M., Bakker, D., Valentin-Weigand, P., van Eden, W. (2001). Differential Changes in Heat Shock Protein-, Lipoarabinomannan-, and Purified Protein Derivative-Specific Immunoglobulin G1 and G2 Isotype Responses during Bovine Mycobacterium avium subsp. paratuberculosis Infection. Infect. Immun. 69: 1492-1498 [Abstract] [Full Text]  
• Astarie-Dequeker, C., Nigou, J., Puzo, G., Maridonneau-Parini, I. (2000). Lipoarabinomannans Activate the Protein Tyrosine Kinase Hck in Human Neutrophils. Infect. Immun. 68: 4827-4830 [Abstract] [Full Text]  
• Garcia, R. C., Banfi, E., Pittis, M. G. (2000). Infection of Macrophage-Like THP-1 Cells with Mycobacterium avium Results in a Decrease in Their Ability to Phosphorylate Nucleolin. Infect. Immun. 68: 3121-3128 [Abstract] [Full Text]  
• Sousa, A. O., Mazzaccaro, R. J., Russell, R. G., Lee, F. K., Turner, O. C., Hong, S., Van Kaer, L., Bloom, B. R. (2000). Relative contributions of distinct MHC class I-dependent cell populations in protection to tuberculosis infection in mice. Proc. Natl. Acad. Sci. USA 97: 4204-4208 [Abstract] [Full Text]  
• Cooper, A. M., Segal, B. H., Frank, A. A., Holland, S. M., Orme, I. M. (2000). Transient Loss of Resistance to Pulmonary Tuberculosis in p47phox-/- Mice. Infect. Immun. 68: 1231-1234 [Abstract] [Full Text]  
• Gilleron, M., Bala, L., Brando, T., Vercellone, A., Puzo, G. (2000). Mycobacterium tuberculosis H37Rv Parietal and Cellular Lipoarabinomannans. CHARACTERIZATION OF THE ACYL- AND GLYCO-FORMS. J. Biol. Chem. 275: 677-684 [Abstract] [Full Text]  
• Glatman-Freedman, A., Mednick, A. J., Lendvai, N., Casadevall, A. (2000). Clearance and Organ Distribution of Mycobacterium tuberculosis Lipoarabinomannan (LAM) in the Presence and Absence of LAM-Binding Immunoglobulin M. Infect. Immun. 68: 335-341 [Abstract] [Full Text]  
• Schaeffer, M. L., Khoo, K.-H., Besra, G. S., Chatterjee, D., Brennan, P. J., Belisle, J. T., Inamine, J. M. (1999). The pimB Gene of Mycobacterium tuberculosis Encodes a Mannosyltransferase Involved in Lipoarabinomannan Biosynthesis. J. Biol. Chem. 274: 31625-31631 [Abstract] [Full Text]  
• Ting, L.-M., Kim, A. C., Cattamanchi, A., Ernst, J. D. (1999). Mycobacterium tuberculosis Inhibits IFN-{gamma} Transcriptional Responses Without Inhibiting Activation of STAT1. J. Immunol. 163: 3898-3906 [Abstract] [Full Text]  
• Ferguson, J. S., Voelker, D. R., McCormack, F. X., Schlesinger, L. S. (1999). Surfactant Protein D Binds to Mycobacterium tuberculosis Bacilli and Lipoarabinomannan via Carbohydrate-Lectin Interactions Resulting in Reduced Phagocytosis of the Bacteria by Macrophages1. J. Immunol. 163: 312-321 [Abstract] [Full Text]  
• Brooks, J. V., Furney, S. K., Orme, I. M. (1999). Metronidazole Therapy in Mice Infected with Tuberculosis. Antimicrob. Agents Chemother. 43: 1285-1288 [Abstract] [Full Text]  
• Glatman-Freedman, A., Casadevall, A. (1998). Serum Therapy for Tuberculosis Revisited: Reappraisal of the Role of Antibody-Mediated Immunity against Mycobacterium tuberculosis. Clin. Microbiol. Rev. 11: 514-532 [Abstract] [Full Text]  
• Johnson, B. J., Estrada, I., Shen, Z., Ress, S., Willcox, P., Colston, M. J., Kaplan, G. (1998). Differential Gene Expression in Response to Adjunctive Recombinant Human Interleukin-2 Immunotherapy in Multidrug-Resistant Tuberculosis Patients. Infect. Immun. 66: 2426-2433 [Abstract] [Full Text]  
• Lin, Y., Zhang, M., Barnes, P. F. (1998). Chemokine Production by a Human Alveolar Epithelial Cell Line in Response to Mycobacterium tuberculosis. Infect. Immun. 66: 1121-1126 [Abstract] [Full Text]  
• George, K. M., Barker, L. P., Welty, D. M., Small, P. L. C. (1998). Partial Purification and Characterization of Biological Effects of a Lipid Toxin Produced by Mycobacterium ulcerans. Infect. Immun. 66: 587-593 [Abstract] [Full Text]  
• Knutson, K. L., Hmama, Z., Herrera-Velit, P., Rochford, R., Reiner, N. E. (1998). Lipoarabinomannan of Mycobacterium tuberculosis Promotes Protein Tyrosine Dephosphorylation and Inhibition of Mitogen-activated Protein Kinase in Human Mononuclear Phagocytes. ROLE OF THE Src HOMOLOGY 2 CONTAINING TYROSINE PHOSPHATASE 1. J. Biol. Chem. 273: 645-652 [Abstract] [Full Text]  
• Bernardo, J., Billingslea, A. M., Blumenthal, R. L., Seetoo, K. F., Simons, E. R., Fenton, M. J. (1998). Differential Responses of Human Mononuclear Phagocytes to Mycobacterial Lipoarabinomannans: Role of CD14 and the Mannose Receptor. Infect. Immun. 66: 28-35 [Abstract] [Full Text]  
• Nigou, J., Gilleron, M., Cahuzac, B., Bounery, J.-D., Herold, M., Thurnher, M., Puzo, G. (1997). The Phosphatidyl-myo-inositol Anchor of the Lipoarabinomannans from Mycobacterium bovis Bacillus Calmette Guerin. HETEROGENEITY, STRUCTURE, AND ROLE IN THE REGULATION OF CYTOKINE SECRETION. J. Biol. Chem. 272: 23094-23103 [Abstract] [Full Text]  
• Besra, G. S., Morehouse, C. B., Rittner, C. M., Waechter, C. J., Brennan, P. J. (1997). Biosynthesis of Mycobacterial Lipoarabinomannan. J. Biol. Chem. 272: 18460-18466 [Abstract] [Full Text]  
• MacMicking, J. D., North, R. J., LaCourse, R., Mudgett, J. S., Shah, S. K., Nathan, C. F. (1997). Identification of nitric oxide synthase as a protective locus against tuberculosis. Proc. Natl. Acad. Sci. USA 94: 5243-5248 [Abstract] [Full Text]  
• Khoo, K.-H., Douglas, E., Azadi, P., Inamine, J. M., Besra, G. S., Brennan, P. J., Chatterjee, D. (1996). Truncated Structural Variants of Lipoarabinomannan in Ethambutol Drug-resistant Strains of Mycobacterium smegmatis. INHIBITION OF ARABINAN BIOSYNTHESIS BY ETHAMBUTOL. J. Biol. Chem. 271: 28682-28690 [Abstract] [Full Text]  
• Sturgill-Koszycki, S, Schlesinger, P., Chakraborty, P, Haddix, P., Collins, H., Fok, A., Allen, R., Gluck, S., Heuser, J, Russell, D. (1994). Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science 263: 678-681 [Abstract]  
• Maiti, D., Bhattacharyya, A., Basu, J. (2001). Lipoarabinomannan from Mycobacterium tuberculosis Promotes Macrophage Survival by Phosphorylating Bad through a Phosphatidylinositol 3-Kinase/Akt Pathway. J. Biol. Chem. 276: 329-333 [Abstract] [Full Text]