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Mycobacterium tuberculosis (Mtb) infects lung myeloid cells, but the specific Mtb-permissive cells and host mechanisms supporting Mtb persistence during chronic infection are incompletely characterized. We report that after the development of T cell responses, CD11clo monocyte-derived cells harbor more live Mtb than alveolar macrophages (AM), neutrophils, and CD11chi monocyte-derived cells. Transcriptomic and functional studies revealed that the lysosome pathway is underexpressed in this highly permissive subset, characterized by less lysosome content, acidification, and proteolytic activity than AM, along with less nuclear TFEB, a regulator of lysosome biogenesis. Mtb infection does not drive lysosome deficiency in CD11clo monocyte-derived cells but promotes recruitment of monocytes that develop into permissive lung cells, mediated by the Mtb ESX-1 secretion system. The c-Abl tyrosine kinase inhibitor nilotinib activates TFEB and enhances lysosome functions of macrophages in vitro and in vivo, improving control of Mtb infection. Our results suggest that Mtb exploits lysosome-poor lung cells for persistence and targeting lysosome biogenesis is a potential host-directed therapy for tuberculosis.

Objective Adaptive human behaviour requires cognitive control ‐ the monitoring of actions and performance, to regulate and coordinate ongoing behaviour. Major depression is associated with neuropsychological differences in cognitive control, however behavioural experiments have failed to consistently reflect this. We explore this discrepancy. Method Two experiments were conducted, in which participants completed an Emotional Stroop task, and the Beck Depression Inventory‐II. In Experiment 1, participants were instructed to judge the font colour of a printed word. The word could have emotional or non‐emotional meaning. In Experiment 2, participants judged the font colour of the word, and also identified whether any letter was italicised. This manipulation was designed to induce errors to facilitate analysis. Results Depression symptoms are linked to severe deficits in cognitive control following errors. In Experiment 1, for emotional words, major depression symptoms were associated with a failure to instigate behavioural adjustments following errors, leading to reduced performance (F(1,25) = 4.61, p = .042). For non‐emotional content, we found major depression symptoms were associated with substantial adjustments following errors, mitigating reduced performance. These findings were replicated in Experiment 2 using a more robust analysis (F(1,30) = 6.45, p = .017). Conclusions These findings suggest that under emotional priming, major depression is marked by a failure to adapt behaviour in response to relevant environmental feedback. This work has implications for interpreting prior and future scientific findings, and may also inform clinical applications for depression treatment.