title: Transcriptional responses of host peripheral blood cells to tuberculosis infection.
abstract: Host responses following exposure to Mycobacterium tuberculosis (TB) are complex and can significantly affect clinical outcome. These responses, which are largely mediated by complex immune mechanisms involving peripheral blood cells (PBCs) such as T-lymphocytes, NK cells and monocyte-derived macrophages, have not been fully characterized. We hypothesize that different clinical outcome following TB exposure will be uniquely reflected in host gene expression profiles, and expression profiling of PBCs can be used to discriminate between different TB infectious outcomes. In this study, microarray analysis was performed on PBCs from three TB groups (BCG-vaccinated, latent TB infection, and active TB infection) and a control healthy group. Supervised learning algorithms were used to identify signature genomic responses that differentiate among group samples. Gene Set Enrichment Analysis was used to determine sets of genes that were co-regulated. Multivariate permutation analysis (p < 0.01) gave 645 genes differentially expressed among the four groups, with both distinct and common patterns of gene expression observed for each group. A 127-probeset, representing 77 known genes, capable of accurately classifying samples into their respective groups was identified. In addition, 13 insulin-sensitive genes were found to be differentially regulated in all three TB infected groups, underscoring the functional association between insulin signaling pathway and TB infection.
authors.affiliation: Walter Reed Army Institute of Research, 503 Robert Grant Avenue, Silver Spring, MD 20910, USA. Emil.Lesho@us.army.mil
authors.forename: Emil
authors.initials: E
authors.lastname: Lesho
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Forestiero
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario D
authors.initials: RD
authors.lastname: Hirata
authors.forename: Leticia
authors.initials: L
authors.lastname: Cecon
authors.forename: Fernando F
authors.initials: FF
authors.lastname: Melo
authors.forename: Sun H
authors.initials: SH
authors.lastname: Paik
authors.forename: Yoko
authors.initials: Y
authors.lastname: Murata
authors.forename: Earl W
authors.initials: EW
authors.lastname: Ferguson
authors.forename: Zhining
authors.initials: Z
authors.lastname: Wang
authors.forename: Guck T
authors.initials: GT
authors.lastname: Ooi
mesh_terms: D000368:Aged; D000942:Antigens, Bacterial / Q000276:immunology*; D016000:Cluster Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D055985:Latent Tuberculosis / Q000276:immunology; D008262:Macrophage Activation / Q000235:genetics / Q000276:immunology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000472:pathogenicity*; D020641:Polymorphism, Single Nucleotide; D011933:Reagent Kits, Diagnostic; D015203:Reproducibility of Results; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D015533:Transcriptional Activation; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology*
chemical_list: D000942:Antigens, Bacterial; D011933:Reagent Kits, Diagnostic