title: Cord factor trehalose 6,6'-dimycolate (TDM) mediates trafficking events during mycobacterial infection of murine macrophages.
abstract: The persistence of tuberculosis within pulmonary granulomatous lesions is a complex phenomenon, with bacterial survival occurring in a focal region of high immune activity. In part, the survival of the organism may be linked to the ability of the surface glycolipid trehalose 6,6'-dimycolate (TDM; cord factor) to inhibit fusion events between phospholipid vesicles inside the host macrophage. At the same time, TDM contributes to macrophage activation and a cascade of events required for initiation and maintenance of granulomatous responses. This allows increased sequestration of organisms and further survival and persistence within host tissues. Bacterial viability, macrophage cytokine and chemokine response, and intracellular trafficking were investigated in Mycobacterium tuberculosis from which TDM had been removed. Removal of surface lipids led to enhanced trafficking of organisms to acidic compartments; reconstitution of delipidated organisms with either pure TDM or the petroleum ether extract containing crude surface lipids restored normal responses. Use of TDM-coated polystyrene beads demonstrated that TDM can mediate intracellular trafficking events, as well as influence macrophage production of pro-inflammatory molecules. Thus, the presence of TDM may be an important determinant for successful infection and survival of M. tuberculosis within macrophages.
authors.affiliation: Department of Pathology and Program in Molecular Pathology, Graduate School of Biomedical Sciences, University of Texas - Houston Health Science Center, Houston, TX, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Indrigo
authors.affiliation: Department of Pathology and Program in Molecular Pathology, Graduate School of Biomedical Sciences, University of Texas - Houston Health Science Center, Houston, TX, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Hunter
authors.affiliation: Department of Pathology and Program in Molecular Pathology, Graduate School of Biomedical Sciences, University of Texas - Houston Health Science Center, Houston, TX, USA.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D000818:Animals; D002460:Cell Line; D003311:Cord Factors / Q000302:isolation & purification / Q000502:physiology / Q000633:toxicity*; D016207:Cytokines / Q000096:biosynthesis; D018836:Inflammation Mediators / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification / Q000472:pathogenicity* / Q000502:physiology; D014397:Tuberculosis, Pulmonary / Q000209:etiology / Q000382:microbiology; D014774:Virulence / Q000502:physiology
chemical_list: D003311:Cord Factors; D016207:Cytokines; D018836:Inflammation Mediators