Gene expression profiles of bronchoalveolar cells in pulmonary TB

Bindu Raju, Yoshihiko Hoshino, Ilana Belitskaya-Lévy, Rod Dawson, Stanley Ress, Jeffrey A. Gold, Rany Condos, Richard Pine, Stuart Brown, Anna Nolan, William N. Rom, Michael D. Weiden

Research output: Contribution to journalArticle

42 Scopus citations

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-γ receptor), and monokine induced by IFN-γ (MIG) expression with increased IFN-γ 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.

Original languageEnglish (US)
Pages (from-to)39-51
Number of pages13
JournalTuberculosis
Volume88
Issue number1
DOIs
StatePublished - Jan 2008

Keywords

  • Bronchoalveolar lavage
  • Functional genomics
  • Human
  • Immunity
  • Tuberculosis

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Microbiology (medical)
  • Infectious Diseases

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    Raju, B., Hoshino, Y., Belitskaya-Lévy, I., Dawson, R., Ress, S., Gold, J. A., Condos, R., Pine, R., Brown, S., Nolan, A., Rom, W. N., & Weiden, M. D. (2008). Gene expression profiles of bronchoalveolar cells in pulmonary TB. Tuberculosis, 88(1), 39-51. https://doi.org/10.1016/j.tube.2007.07.003