Mycobacterial lipoarabinomannan inhibits gamma interferon-mediated activation of macrophages
- PMID: 3128482
- PMCID: PMC259795
- DOI: 10.1128/iai.56.5.1232-1236.1988
Mycobacterial lipoarabinomannan inhibits gamma interferon-mediated activation of macrophages
Abstract
The principal efferent role of the macrophage in acquired resistance to intracellular pathogens depends on activation by T-cell lymphokines, primarily gamma interferon (IFN-gamma). However, mouse macrophages that are heavily burdened with Mycobacterium leprae are refractory to activation by IFN-gamma and are thus severely compromised in their capacity for both enhanced microbicidal and tumoricidal activities. We report here that lipoarabinomannan (LAM), a highly immunogenic lipopolysaccharide that is a prominent component of the cell walls of M. leprae and M. tuberculosis, was a potent inhibitor of IFN-gamma-mediated activation of mouse macrophages in vitro. Inhibition of macrophage activation by LAM required preincubation for approximately 24 h, resulting in uptake of LAM into cytoplasmic vacuoles of macrophages. Intact LAM was necessary to inhibit IFN-gamma-mediated activation, as this property was lost when the acyl side chains were removed from LAM by mild alkaline hydrolysis. In addition, LAM was an abundant constituent of macrophages isolated from lepromatous granulomas of M. leprae-infected nude mice and likely contributed to the defective activation of granuloma macrophages by IFN-gamma.
Similar articles
-
Inhibition of interferon-gamma-mediated activation in mouse macrophages treated with lipoarabinomannan.Clin Exp Immunol. 1990 Apr;80(1):141-8. doi: 10.1111/j.1365-2249.1990.tb06454.x. Clin Exp Immunol. 1990. PMID: 2138940 Free PMC article.
-
Regulation of murine macrophage effector functions by lipoarabinomannan from mycobacterial strains with different degrees of virulence.Infect Immun. 1993 Oct;61(10):4173-81. doi: 10.1128/iai.61.10.4173-4181.1993. Infect Immun. 1993. PMID: 8406806 Free PMC article.
-
Induction of unresponsiveness to gamma interferon in macrophages infected with Mycobacterium leprae.Infect Immun. 1988 Aug;56(8):1912-9. doi: 10.1128/iai.56.8.1912-1919.1988. Infect Immun. 1988. PMID: 2840398 Free PMC article.
-
Macrophage activation: lipoarabinomannan from avirulent and virulent strains of Mycobacterium tuberculosis differentially induces the early genes c-fos, KC, JE, and tumor necrosis factor-alpha.J Immunol. 1993 Mar 1;150(5):1886-96. J Immunol. 1993. PMID: 8436823
-
Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response.Mol Microbiol. 2004 Jul;53(2):391-403. doi: 10.1111/j.1365-2958.2004.04183.x. Mol Microbiol. 2004. PMID: 15228522 Review.
Cited by
-
Vaccination of mice with a soluble protein fraction of Mycobacterium leprae provides consistent and long-term protection against M. leprae infection.Infect Immun. 1992 May;60(5):1840-4. doi: 10.1128/iai.60.5.1840-1844.1992. Infect Immun. 1992. PMID: 1563772 Free PMC article.
-
Lymphoproliferative response and its relationship with histological lesions in experimental ovine paratuberculosis and its diagnostic implications.Vet Res Commun. 2008 Jan;32(1):107-19. doi: 10.1007/s11259-007-9008-8. Epub 2007 Jul 6. Vet Res Commun. 2008. PMID: 17619156
-
Expression and characterization of the Mycobacterium tuberculosis serine/threonine protein kinase PknB.Infect Immun. 1999 Nov;67(11):5676-82. doi: 10.1128/IAI.67.11.5676-5682.1999. Infect Immun. 1999. PMID: 10531215 Free PMC article.
-
Hansen's disease.West J Med. 1993 Jun;158(6):583-90. West J Med. 1993. PMID: 8337852 Free PMC article. Review. No abstract available.
-
Lipoarabinomannans: characterization of the multiacylated forms of the phosphatidyl-myo-inositol anchor by NMR spectroscopy.Biochem J. 1999 Feb 1;337 ( Pt 3)(Pt 3):453-60. Biochem J. 1999. PMID: 9895288 Free PMC article.
References
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources