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Trehalose 6,6′ dimycolate (TDM) and Lipid in the Pathogenesis of Caseating Granulomas of Tuberculosis in Mice
Author(s) -
Hunter Robert L,
Olsen Martaret,
Jagannath Chinnaswamy,
Actor Jeffrey K
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a214-c
Subject(s) - tuberculosis , lipid droplet , toxicity , chemistry , macrophage , inflammation , pathogenesis , tumor necrosis factor alpha , pathology , microbiology and biotechnology , biochemistry , biology , immunology , medicine , in vitro , organic chemistry
Trehalose 6,6′ dimycolate (TDM) is the most abundant, most granulomagenic and most toxic lipid extractable from the surface of virulent M. tuberculosis (MTB). Its toxicity requires activation by oily surfaces. Injections of MTB and/or TDM into sensitized mice induced caseating granulomas that centered on oil droplets. If large doses of MTB were injected in saline, caseating granulomas developed in adipose tissue. MTB with surface TDM removed induced only acute inflammation and did not persist. Variations in protocols produced several variants of caseating granulomas each with characteristics of human tuberculosis. In each instance, MTB were localized in fat cells or oil drops during initiation of caseating granulomas suggesting that necrosis was caused by activation of the toxicity of TDM. Evidence extending these findings to the lung was derived from the observation that in sensitized mice, as in humans, developing tuberculosis stimulates accumulation of lipid selectively in alveoli. MTB preferentially associated with lipid droplets in developing necrotic foci in late stage murine tuberculosis. This supports the hypothesis that pulmonary tuberculosis sequesters MTB in a protected environment that accumulates lipid until it is able to activate the toxicity of TDM and initiate necrosis that results in caseating granulomas.