(i) Aerosolized Mtb is initially contained within lung granulomas where it can remain quiescent or cause progressive pulmonary disease with unrestricted bacterial replication. (ii) In some cases, tissue destruction leads to pulmonary cavitation, which is associated with high mycobacterial burden and poor drug penetration, increasing the risk for transmission and emergent drug resistance. Mtb infection induces MMPs, which regulate inflammatory processes that range from tissue remodeling to tissue destruction (25) and are linked to granuloma maintenance and Mtb dissemination (10–12). MMPs also degrade elastin and collagen, contributing to cavitation (13). (iii) Hao Miow et al. explored the effects of doxycycline when added to standard antituberculous therapy in a randomized, placebo-controlled trial of patients with newly diagnosed pulmonary TB (23). Relative to healthy controls, multiple inflammatory gene programs were enriched among pulmonary TB subjects including coexpression modules related to extracellular matrix (ECM) genes. Longitudinal analysis of blood transcriptomes indicated doxycycline reduced transcription of MMP9 and genes related to interferon (IFN) signaling and the innate immune response. These findings mirrored lower levels of MMP proteins in serum (iv) and and lower MMP-1, -8, -9, -12, -13 levels in sputum (ii). This correlated with decreased elastase (potentially including MMP-9 and -12) and collagenase (potentially including MMP-1, -8, -13) enzyme activities in sputum. While the study was underpowered to detect more relevant clinical or microbiologic outcomes, the broad MMP effects of doxycycline correlated with reduced lung cavity volumes (v) at two months, which is notable considering doxycycline was dosed only during the initial two weeks.