Abstract
Infection of bovines with Mycobacterium bovis causes important financial hardship in many countries presenting also a risk for humans. M. bovis is known to be adapted to survive and thrive within the intramacrophage environment. In spite of its relevance, at present the information about macrophage expression patterns is scarce, particularly regarding the bovine host. In this study, transcriptomic analysis was used to detect genes differentially expressed in macrophages derived from peripheral blood mononuclear cells at early stages of infection with two Argentinean strains of M. bovis, a virulent and an attenuated strains. The results showed that the number of differentially expressed genes in the cells infected with the virulent strain (5) was significantly lower than those in the cells infected with the attenuated strain (172). Several genes were more strongly expressed in infected macrophages. Among them, we detected encoding transcription factors, anthrax toxin receptor, cell division and apoptosis regulator, ankyrin proteins, cytoskeleton proteins, protein of cell differentiation, and regulators of endocytic traffic of membrane. Quantitative real-time PCR of a selected group of differentially expressed genes confirmed the microarrays results. Altogether, the present results contribute to understanding the mechanisms involved in the early interaction of M. bovis with the bovine macrophage.
Highlights
Mycobacterium bovis is an important aerobic pathogenic bacterium and the causative agent of most cases of tuberculosis in bovines (BTB)
Comprehensive gene expression pro les for the three attenuated and the three virulent M. bovis macrophage infections were generated with high-density oligonucleotide bovine arrays (Affymetrix) and 24,072 probe sets, which in total interrogated the expression levels of approximately 23,000 transcripts
The number of differentially expressed genes in the cells infected with the virulent strain (5) was signi cantly less than those in the cells infected with the attenuated strain (172)
Summary
Mycobacterium bovis is an important aerobic pathogenic bacterium and the causative agent of most cases of tuberculosis in bovines (BTB). E pathogenesis of BTB results from a complex interaction between the pathogen and the host [3]. In response to factors that are still unknown, the population of bacteria begins replication and escapes the infected macrophages causing illness in a small proportion of individuals. Innate immunity provides an important early defense against M. bovis and is critical in determining the clinical outcome. In order to survive the immune response, mycobacteria have developed a variety of mechanisms that prevent them from being killed by their host cells [4]. The level of pathogenicity of mycobacterial species in different hosts can be related to their effects on the host’s immune response.
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