Leprosy, caused primarily by Mycobacterium leprae , is considered a disease introduced into the Americas during European colonization. However, the recent discovery of a second pathogen causing leprosy, M. lepromatosis , mainly found in the Americas, challenges this view. Here, we show that M. lepromatosis infected humans in the Americas before European contact. By screening 389 ancient and 408 contemporary samples, we have expanded the genetic data available for the species. Phylogenetic analyses revealed distinct human-infecting clades of M. lepromatosis , with one dominating North America since colonial times. The presence of millennia-old strains in North and South America indicates that M. lepromatosis may have been widespread during the Late Holocene, demonstrating that M. lepromatosis leprosy has a long-standing history in the Americas before European arrival.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, is a leading cause of morbidity worldwide. Along with CD4+ T lymphocytes, macrophages serve as key pillars of the immune response against this intracellular pathogen, which is essential for the prompt and effective elimination of the bacilli. Many strategies have been developed to enhance the microbicidal performance of macrophages; among them, stimulation with polymeric microparticles is one of the most promising. Exposition of infected macrophages to these microparticles may enhance non-specific innate immune mechanisms such as the promotion of phagocytosis, the induction of proinflammatory cytokines, and the production of reactive oxygen intermediates (ROI), contributing to the elimination of mycobacteria. Here, we evaluated the in vitro effect of starch microparticles (SMPs) on the activation and microbicidal activity of infected alveolar macrophages. The results demonstrate that these alpha-glucan microparticles are efficiently phagocytosed by infected macrophages and promote cellular activation, inducing reactive oxygen and nitrogen species, moderate apoptosis, and modulating cytokine and chemokine production without causing an excessive proinflammatory response. These effects contributed to the elimination of tubercle bacilli when SMPs were administered after infection, suggesting their usefulness as a post-exposure treatment that activates macrophages against the pathogen.