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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism
EMBO Molecular Medicine, Volume 2, No. 7, Year 2010
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Description
The progression of human tuberculosis (TB) to active disease and transmission involves the development of a caseous granuloma that cavitates and releases infectious Mycobacterium tuberculosis bacilli. In the current study, we exploited genome-wide microarray analysis to determine that genes for lipid sequestration and metabolism were highly expressed in caseous TB granulomas. Immunohistological analysis of these granulomas confirmed the disproportionate abundance of the proteins involved in lipid metabolism in cells surrounding the caseum; namely, adipophilin, acyl-CoA synthetase long-chain family member 1 and saposin C. Biochemical analysis of the lipid species within the caseum identified cholesterol, cholesteryl esters, triacylglycerols and lactosylceramide, which implicated low-density lipoprotein-derived lipids as the most likely source. M. tuberculosis infection in vitro induced lipid droplet formation in murine and human macrophages. Furthermore, the M. tuberculosis cell wall lipid, trehalose dimycolate, induced a strong granulomatous response in mice, which was accompanied by foam cell formation. These results provide molecular and biochemical evidence that the development of the human TB granuloma to caseation correlates with pathogen-mediated dysregulation of host lipid metabolism. © 2010 EMBO Molecular Medicine.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2913288/bin/emmm0002-0258-SD1.pdf
Authors & Co-Authors
Kim, Mi Jeong
United States, Ithaca
Cornell University
Wainwright, Helen Cecilia
South Africa, Cape Town
Faculty of Health Sciences
Locketz, Michael
South Africa, Cape Town
Faculty of Health Sciences
Bekker, Linda-Gail Gail
South Africa, Cape Town
University of Cape Town
Walther, Gabi B.
South Africa, Observatory
Groote Schuur Hospital
Germany, Munich
Technische Universität München
Dittrich, Corneli
South Africa, Cape Town
Faculty of Health Sciences
Visser, Annalie
South Africa, Cape Town
Faculty of Health Sciences
Wang, Wei
United States, Ithaca
Cornell University
Hsu, Fong Fu
United States, St. Louis
Washington University School of Medicine in St. Louis
Wiehart, Ursula
United States, Ithaca
Cornell University
South Africa, Bellville
University of the Western Cape
Tsenova, Liana
United States, Newark
Rutgers Biomedical and Health Sciences
South Africa, Bellville
University of the Western Cape
Kaplan, Gilla
United States, Newark
Rutgers Biomedical and Health Sciences
Russell, David G.
South Africa, Cape Town
Faculty of Health Sciences
Statistics
Citations: 419
Authors: 13
Affiliations: 8
Identifiers
Doi:
10.1002/emmm.201000079
ISSN:
17574676
e-ISSN:
17574684
Research Areas
Health System And Policy
Infectious Diseases