Global Tuberculosis Report 2024 (WHO, 2024).
Barber, D. L. et al. Tuberculosis following PD-1 blockade for cancer immunotherapy. Sci. Transl. Med. 11, eaat2702 (2019).
Kauffman, K. D. et al. PD-1 blockade exacerbates Mycobacterium tuberculosis infection in rhesus macaques. Sci. Immunol. 6, eabf3861 (2021).
Lei, Z., Wang, J. & Liu, C. H. Developing next-generation tuberculosis vaccines based on pathogen–host interactions: towards a holistic perspective. hLife 3, 164–171 (2025).
Flynn, J. L. & Chan, J. Immune cell interactions in tuberculosis. Cell 185, 4682–4702 (2022).
Davis, J. M. & Ramakrishnan, L. The role of the granuloma in expansion and dissemination of early tuberculous infection. Cell 136, 37–49 (2009).
Urdahl, K. B. Understanding and overcoming the barriers to T cell-mediated immunity against tuberculosis. Semin. Immunol. 26, 578–587 (2014).
Ashenafi, S. & Brighenti, S. Reinventing the human tuberculosis (TB) granuloma: learning from the cancer field. Front. Immunol. 13, 1059725 (2022).
McCaffrey, E. F. et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat. Immunol. 23, 318–329 (2022).
Sawyer, A. J. et al. Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis. J. Exp. Med. 220, e20221392 (2023).
Merritt, C. R. et al. Multiplex digital spatial profiling of proteins and RNA in fixed tissue. Nat. Biotechnol. 38, 586–599 (2020).
Chai, Q. et al. Lung gene expression signatures suggest pathogenic links and molecular markers for pulmonary tuberculosis, adenocarcinoma and sarcoidosis. Commun. Biol. 3, 604 (2020).
Heid, H. W., Moll, R., Schwetlick, I., Rackwitz, H. R. & Keenan, T. W. Adipophilin is a specific marker of lipid accumulation in diverse cell types and diseases. Cell Tissue Res. 294, 309–321 (1998).
Driver, E. R. et al. Evaluation of a mouse model of necrotic granuloma formation using C3HeB/FeJ mice for testing of drugs against Mycobacterium tuberculosis. Antimicrob. Agents Chemother. 56, 3181–3195 (2012).
Tarling, E. J., de Aguiar Vallim, T. Q. & Edwards, P. A. Role of ABC transporters in lipid transport and human disease. Trends Endocrinol. Metab. 24, 342–350 (2013).
Chow, A., Toomre, D., Garrett, W. & Mellman, I. Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane. Nature 418, 988–994 (2002).
Knight, M., Braverman, J., Asfaha, K., Gronert, K. & Stanley, S. Lipid droplet formation in Mycobacterium tuberculosis infected macrophages requires IFN-γ/HIF-1α signaling and supports host defense. PLoS Pathog. 14, e1006874 (2018).
Bosch, B., Heipertz, E. L., Drake, J. R. & Roche, P. A. Major histocompatibility complex (MHC) class II-peptide complexes arrive at the plasma membrane in cholesterol-rich microclusters. J. Biol. Chem. 288, 13236–13242 (2013).
Kim, M. J. et al. Caseation of human tuberculosis granulomas correlates with elevated host lipid metabolism. EMBO Mol. Med. 2, 258–274 (2010).
Rigamonti, E. et al. Liver X receptor activation controls intracellular cholesterol trafficking and esterification in human macrophages. Circ. Res. 97, 682–689 (2005).
Lu, F. R. et al. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection. Elife 4, e12177 (2015).
Wagstaff, A. J. & Zellweger, J. P. T.-S. P. O. T. TB: an in vitro diagnostic assay measuring T-cell reaction to Mycobacterium tuberculosis-specific antigens. Mol. Diagn. Ther. 10, 57–63 (2006).
Ashouri, J. F. & Weiss, A. Endogenous Nur77 is a specific indicator of antigen receptor signaling in human T and B cells. J. Immunol. 198, 657–668 (2017).
Pfeffer, S. R. NPC intracellular cholesterol transporter 1 (NPC1)-mediated cholesterol export from lysosomes. J. Biol. Chem. 294, 1706–1709 (2019).
Sallese, A. et al. Targeting cholesterol homeostasis in lung diseases. Sci. Rep. 7, 10211 (2017).
McCarthy, C. et al. Statin as a novel pharmacotherapy of pulmonary alveolar proteinosis. Nat. Commun. 9, 3127 (2018).
Lu, Y. J. et al. CD4 T cell help prevents CD8 T cell exhaustion and promotes control of Mycobacterium tuberculosis infection. Cell Rep. 36, 109696 (2021).
Losslein, A. K. et al. Monocyte progenitors give rise to multinucleated giant cells. Nat. Commun. 12, 2027 (2021).
Gao, X., Liu, C. & Wang, S. Mucosal immune responses in the lung during respiratory infection: the organization and regulation of iBALT structure. hLife 1, 71–82 (2023).
Peyron, P. et al. Foamy macrophages from tuberculous patients’ granulomas constitute a nutrient-rich reservoir for M. tuberculosis persistence. PLoS Pathog. 4, e1000204 (2008).
Daniel, J., Maamar, H., Deb, C., Sirakova, T. D. & Kolattukudy, P. E. Mycobacterium tuberculosis uses host triacylglycerol to accumulate lipid droplets and acquires a dormancy-like phenotype in lipid-loaded macrophages. PLoS Pathog. 7, e1002093 (2011).
Dawa, S. et al. Inhibition of granuloma triglyceride synthesis imparts control of Mycobacterium tuberculosis through curtailed inflammatory responses. Front. Immunol. 12, 722735 (2021).
Thorson, L. M., Doxsee, D., Scott, M. G., Wheeler, P. & Stokes, R. W. Effect of mycobacterial phospholipids on interaction of Mycobacterium tuberculosis with macrophages. Infect. Immun. 69, 2172–2179 (2001).
Roy, K., Mandloi, S., Chakrabarti, S. & Roy, S. Cholesterol corrects altered conformation of MHC-II protein in Leishmania donovani infected macrophages: implication in therapy. PLoS Negl. Trop. Dis. 10, e0004710 (2016).
Komaniwa, S. et al. Lipid-mediated presentation of MHC class II molecules guides thymocytes to the CD4 lineage. Eur. J. Immunol. 39, 96–112 (2009).
Chai, Q. et al. A bacterial phospholipid phosphatase inhibits host pyroptosis by hijacking ubiquitin. Science 378, eabq0132 (2022).
Kaushal, D. et al. Mucosal vaccination with attenuated Mycobacterium tuberculosis induces strong central memory responses and protects against tuberculosis. Nat. Commun. 6, 8533 (2015).
Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).
Newman, A. M. et al. Robust enumeration of cell subsets from tissue expression profiles. Nat. Methods 12, 453–457 (2015).
Chen, Z. et al. Inference of immune cell composition on the expression profiles of mouse tissue. Sci. Rep. 7, 40508 (2017).
Sikkema, L. et al. An integrated cell atlas of the lung in health and disease. Nat. Med. 29, 1563–1577 (2023).
Tabula Muris, C. A single-cell transcriptomic atlas characterizes ageing tissues in the mouse. Nature 583, 590–595 (2020).
Yu, G., Wang, L. G., Han, Y. & He, Q. Y. clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS 16, 284–287 (2012).
Hanzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics 14, 7 (2013).
Browaeys, R., Saelens, W. & Saeys, Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat. Methods 17, 159–162 (2020).
Futschik, M. E. & Carlisle, B. Noise-robust soft clustering of gene expression time-course data. J. Bioinform. Comput. Biol. 3, 965–988 (2005).
Harari, A. et al. Dominant TNF-α+ Mycobacterium tuberculosis-specific CD4+ T cell responses discriminate between latent infection and active disease. Nat. Med. 17, 372–376 (2011).
Thelen, K. M. et al. Brain cholesterol synthesis in mice is affected by high dose of simvastatin but not of pravastatin. J. Pharmacol. Exp. Ther. 316, 1146–1152 (2006).
King, E. M., Hume, P. S., Janssen, W. J. & McCubbrey, A. L. Isolation and analysis of macrophage subsets from the mouse and human lung. Methods Mol. Biol. 2506, 257–267 (2022).
Chai, Q. et al. A Mycobacterium tuberculosis surface protein recruits ubiquitin to trigger host xenophagy. Nat. Commun. 10, 1973 (2019).
