Differences of gene expression in bovine alveolar macrophages infected with virulent and attenuated isogenic strains of Mycobacterium bovis.

Infection with Mycobacterium bovis is a significant human and animal health problem in many parts of the world. The first stage of pulmonary tuberculosis occurs after inhalation of the bacilli into an alveolus where they are ingested by resident macrophages. DNA microarray analysis was used to detect genes expressed in bovine lung alveolar macrophages infected with two isogenic strains of M. bovis, a virulent strain, ATCC35723 and an attenuated strain, WAg520 derived from ATCC35723. Chemokines, interleukin-8 and monocyte chemotactic protein 1, were more strongly expressed in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Conversely, a group of genes, including fibrinogen-like protein 2 and legumain, were expressed at a higher level in macrophages infected with WAg520 compared to ATCC35723. Quantitative real-time PCR of a selected group of these differentially expressed genes confirmed enhanced levels of IL-8 mRNA in ATCC35723-infected macrophages compared to WAg520-infected macrophages. Microarray analysis of gene expression in macrophages infected with attenuated isogenic strains of M. bovis may identify key genes involved in early and protective immune responses to tuberculosis.