RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis

Mycobacterium tuberculosis is an intracellular pathogen of macrophages which are key to controlling infection. Inflammatory lesions infected with M. tuberculosis have an acidic extracellular microenvironment which may influence macrophage function. In this study we performed RNA-seq on primary human monocyte derived macrophages from 4 healthy donors infected with virulent M. tuberculosis H37Rv for 24 hours. Cells were infected in media at physiological pH 7.4 or acidic media pH 7.0. Appropriate uninfected control cells at pH 7.4 and pH 7.0 were also included. We were thus able to identify the principal genes and pathways regulated by M. tuberculosis infection and the influence of extracellular acidosis on these pathways. Specifically, we show that acidosis enhances transcription of matrix metalloproteinase genes and increases tissue destruction pathways in tuberculosis. RNA-seq analysis of human monocyte derived macrophages infected with Mycobacterium tuberculosis H37Rv in the presence of extracellular acidosis