medRxiv preprint doi: https://doi.org/10.1101/2020.09.14.20194043; this version posted September 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license . Variations in human monocyte-derived macrophage antimicrobial activities and their associations with tuberculosis clinical manifestations 1 Trinh T. B. Tram1, Vu T. N. Ha1, Do D. A. Thu1, Tran D. Dinh1, Hoang N. Nhung1, Nguyen T. 2 Hanh1, Nguyen H. Phu1, Guy E. Thwaites1,2, Nguyen T. T. Thuong1,2* 3 1Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam 4 2Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of 5 Oxford, Oxford, United Kingdom 6 * Correspondence: 7 Nguyen T. T. Thuong 8
[email protected] 9 Keywords: tuberculosis, acidification, proteolysis, human macrophage, variation 10 Abstract 11 Macrophages play a significant role in preventing infection through antimicrobial activities, 12 particularly acidification and proteolysis. Mycobacterium tuberculosis infection can lead to diverse 13 outcomes, from latent asymptomatic infection to active disease involving multiple organs. Monocyte- 14 derived macrophage is one of the main cell types accumulating in lungs following Mtb infection. The 15 variation of intracellular activities of monocyte-derived macrophages in humans and the influence of 16 these activities on the tuberculosis (TB) spectrum are not well understood. By exploiting ligand- 17 specific bead-based assays, we investigated macrophage antimicrobial activities real-time in healthy 18 volunteers (n=53) with 35 cases of latent TB (LTB), and those with active TB (ATB) and either 19 pulmonary TB (PTB, n=70) or TB meningitis (TBM, n=77).