title: Gene expression profiles of bronchoalveolar cells in pulmonary TB.
abstract: The host response to Mycobacterium tuberculosis includes macrophage activation, inflammation with increased immune effector cells, tissue necrosis, and cavity formation, and fibrosis, distortion, and bronchiectasis. To evaluate the molecular basis of the immune response in the lungs of patients with active pulmonary tuberculosis (TB), we used bronchoalveolar lavage to obtain cells at the site of infection. Affymetrix GeneChip microarrays and cDNA nylon filter microarrays interrogated gene expression in bronchoalveolar lavage (BAL) cells from 11 healthy controls and 17 patients with active pulmonary TB. We found altered gene expression for 69 genes in TB versus normal controls that included cell surface markers, cytokines, chemokines, receptors, transcription factors, and complement components. In addition, TB BAL cell gene expression patterns segregated into 2 groups: one suggestive of a T helper type 1 (Th1) cellular immune response with increased signal transducer and activator of transcription-4 (STAT-4), interferon-gamma (IFN-gamma receptor), and monokine induced by IFN-gamma (MIG) expression with increased IFN-gamma protein levels in BAL fluid; the other group displayed characteristics of Th2 immunity with increased STAT-6, CD81, and IL-10 receptor expression. We were able to demonstrate that a Th2 presentation could change to a Th1 pattern after anti-tuberculous treatment in 1 TB patient studied serially. These gene expression data support the conclusion that pulmonary TB produces a global change in the BAL cell transcriptome with manifestations of either Th1 or Th2 immunity.
authors.affiliation: Department of Medicine, Bellevue Chest Service and Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, 550 First Avenue, NB 7N-24, New York, NY 10016, USA.
authors.forename: Bindu
authors.initials: B
authors.lastname: Raju
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Hoshino
authors.forename: Ilana
authors.initials: I
authors.lastname: Belitskaya-Lévy
authors.forename: Rod
authors.initials: R
authors.lastname: Dawson
authors.forename: Stanley
authors.initials: S
authors.lastname: Ress
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gold
authors.forename: Rany
authors.initials: R
authors.lastname: Condos
authors.forename: Richard
authors.initials: R
authors.lastname: Pine
authors.forename: Stuart
authors.initials: S
authors.lastname: Brown
authors.forename: Anna
authors.initials: A
authors.lastname: Nolan
authors.forename: William N
authors.initials: WN
authors.lastname: Rom
authors.forename: Michael D
authors.initials: MD
authors.lastname: Weiden
mesh_terms: D000328:Adult; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology* / Q000276:immunology; D016207:Cytokines / Q000032:analysis; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D046228:Microarray Analysis; D009169:Mycobacterium tuberculosis / Q000235:genetics; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines