title: Evidence for a unique species-specific hypersensitive epitope in Mycobacterium tuberculosis derived cord factor.
abstract: Presensitization with Mtb-derived trehalose 6,6'-dimycolate (TDM; cord factor) followed by challenge with the same glycolipid species resulted in elicitation of stronger inflammatory responses than when mice were similarly challenged with M. bovis-derived TDM. Mice presensitized to the homologous Mtb-derived TDM demonstrated cachexic over a 6 day period, whereas similarly presensitized mice challenged with the M. bovis-derived TDM, or with emulsion control, did not experience weight loss. Examination of inflammatory responses demonstrated increased lung histopathology in the Mtb-derived TDM challenged group, evidenced by severe tissue disruption, cellular influx, vascular occlusion and lymphocytic cuffing, and endothelial cell damage. Histological analysis demonstrated that lung pathology in the M. bovis challenged group was strikingly similar to that of the acute model challenge. Examination of proinflammatory mediators also showed findings consistent with histological manifestation, with significantly elevated TNF-α and IL-1β, as well as IFN-γ, in the homologous TDM challenged group relative to all other groups. Overall, these findings indicate a difference in hypersensitive immune responses to TDM derived from different mycobacterial strains. Development of specific adaptive immune responses to the Mtb-derived TDM were demonstrated that had limited cross-reactivity to that of M. bovis, thus strongly suggesting the presence of hypersensitive epitopes exclusive to Mtb TDM not present on M. bovis-derived TDM.
authors.affiliation: Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX; Scholarly Concentration in Molecular and Translational Medicine, Houston, TX.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: McMullen
authors.affiliation: Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX.
authors.forename: Shen-An
authors.initials: SA
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX; Scholarly Concentration in Molecular and Translational Medicine, Houston, TX.
authors.forename: Kelly
authors.initials: K
authors.lastname: O'Shea
authors.affiliation: Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX; MD/PhD Program at the Graduate School of Biomedical Sciences at Houston, Houston, TX.
authors.forename: Maureen L
authors.initials: ML
authors.lastname: Aliru
authors.affiliation: Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX; MD/PhD Program at the Graduate School of Biomedical Sciences at Houston, Houston, TX. Electronic address: Jeffrey.K.Actor@uth.tmc.edu.
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D003311:Cord Factors / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D006968:Hypersensitivity, Delayed; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology
chemical_list: D001426:Bacterial Proteins; D003311:Cord Factors; D000939:Epitopes
keywords: Cord factor; Hypersensitivity; Trehalose 6,6′-dimycolate; Tuberculosis TDM