Cord factor

Cord factor refers to trehalose dimycolate, a virulence factor and glycolipid cell-wall component of virulent strains of Mycobacterium tuberculosis and closely related species.[1][2] It is a surface glycolipid which blocks macrophage activation by IFN-γ, induces secretion of TNFα and causes Mycobacterium tuberculosis to form cords in vitro. This is the main virulence factor for the mycobacterium tuberculosis that makes it resistance to anti-tuberculosis medications.

Structure

Trehalose-6,6' dimycolate molecules comprises trehalose sugar esterified into two mycolic acid residues which range from 20–80 carbons in length.[3]

Biological Function

Interaction with host immune system

See also

Technical Note In vitro stimulation of macrophages Purified cord factor was used to stimulate either mouse RAW 264.7 cells or bone marrow-derived macrophages. Cord factor was suspended at a concentration of 1 mg/ml in isopropanol and sonicated in a bath sonicator (model 3510; Branson Ultrasonic Corporation) for 5 min. This suspension was then incubated at 60°C for 10 min. and sonication repeated. The resulting solution was layered onto 24-well tissue culture plates at the indicated concentrations and incubated at 37°C in order to ensure complete evaporation of the solvent. Control wells were layered with solvent without cord factor and incubated at 37°C. To this layer of cord factor, either RAW 264.7 cells or bone marrow- derived macrophages were added at a concentration of 106 cells in 100 μl of medium and incubated at 37°C for 24 hours before activation e.g. TNF-α production was measured in the supernatant. Alternatively, cord factor was suspended at a concentration of 0.2 or 2 mg/ml in hexane. Of the resulting solution 50 μl was layered onto 96-well tissue culture plates at the indicated concentrations of 1 or 10 μg/well, respectively and the solvent completely evaporated. Control wells were layered with solvent without cord factor and incubated at 37°C. To this layer of cord factor, either RAW 264.7 cells or bone marrow-derived macrophages were added at a concentration of 106 cells in 100 μl of medium and incubated at 37°C for 24 hours before activation e.g. TNF-α production was measured in the supernatant. In vivo pulmonary granuloma formation in mice For in vivo experiments 10 μg cord factor per mouse was applied i.v. in a water/ oil/water emulsion. LIT: Interferon-gamma independent formation of pulmonary granuloma in mice by injections with trehalose dimycolate (cord factor), lipoarabinomannan and phosphatidylinositol mannosides isolated from Mycobacterium tuberculosis: H. Takimoto, et al.; Clin. Exp. Immunol. 144, 134 (2006) 􀂃 Macrophage scavenger receptor downregulates mycobacterial cord factor-induced proinflammatory cytokine production by alveolar and hepatic macrophages: Y. Ozeki, et al.; Microb. Pathog. 40, 171 (2006)

References


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