Dual host-pathogen RNA sequencing of wild-type and EZH2-deficient Hoxb8-derived macrophages during Mycobacterium tuberculosis infection

Polycomb repressive complex 2 (PRC2) and its catalytic subunit EZH2 regulate macrophage permissiveness to intracellular Mycobacterium tuberculosis (Mtb). To define the host and bacterial transcriptional responses associated with EZH2 loss, we performed dual host-pathogen RNA sequencing of parental Cas9-expressing Hoxb8-derived macrophages and CRISPR-generated EZH2-deficient macrophages under uninfected conditions and at 3 days after infection with Mtb Erdman smyc'::mCherry. Host and pathogen transcriptomes were quantified to identify macrophage programs associated with bacterial restriction and bacterial stress-adaptation responses.