title: Immune response to Mycobacterium tuberculosis and identification of molecular markers of disease.
abstract: The complex molecular events that occur within the host during the establishment of a Mycobacterium tuberculosis infection are poorly defined, thus preventing identification of predictive markers of disease progression and state. To identify such molecular markers during M. tuberculosis infection, global changes in transcriptional response in the host were assessed using mouse whole genome arrays. Bacterial load in the lungs, the lesions associated with infection, and gene expression profiling was performed by comparing normal lung tissue to lungs from mice collected at 20, 40, and 100 days after aerosol infection with the H37Rv strain of M. tuberculosis. Quantitative, whole lung gene expression identified signature profiles defining different signaling pathways and immunological responses characteristic of disease progression. This includes genes representing members of the interferon-associated gene families, chemokines and cytokines, MHC, and NOS2, as well as an array of cell surface markers associated with the activation of T cells, macrophages, and dendritic cells that participate in immunity to M. tuberculosis infection. More importantly, several gene transcripts encoding proteins that were not previously associated with the host response to M. tuberculosis infection, and unique molecular markers associated with disease progression and state, were identified.
authors.affiliation: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Gonzalez-Juarrero
authors.forename: Luke C
authors.initials: LC
authors.lastname: Kingry
authors.forename: Diane J
authors.initials: DJ
authors.lastname: Ordway
authors.forename: Marcela
authors.initials: M
authors.lastname: Henao-Tamayo
authors.forename: Marisa
authors.initials: M
authors.lastname: Harton
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Basaraba
authors.forename: William H
authors.initials: WH
authors.lastname: Hanneman
authors.forename: Ian M
authors.initials: IM
authors.lastname: Orme
authors.forename: Richard A
authors.initials: RA
authors.lastname: Slayden
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007371:Interferon-gamma / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D015415:Biomarkers; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
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