Adaptive immunity shapes baseline pImmunity Shapes Baseline Physiology of M. Tuberculosistuberculosis in High-Dose Versus Low-Dose I in high-dose versus low-dose infection BALB/c mouse drug treatment mMouse Drug Treatment Models

Around day 16 of infection with Mycobacterium tuberculosis (Mtb), the BALB/c mouse adaptive immunity activates to combat the infection. Usual dual RNA-seq, we investigated the transcriptional changes that occur in both mouse host and Mtb pathogen during an untreated low dose aerosol (LDA) infection—focusing on the transition from innate to adaptive immunity. We found that the onset of adaptive immunity coincided with a rapid reprogramming of Mtb physiology, characterized by suppressed respiration, metabolism, and biosynthesis, together with induction of stress and nutrient acquisition pathways. Changes in key Mtb processes were concordant with changes in host expression of canonical features of adaptive immunity.