WHO. Global Tuberculosis Report (World Health Organization, 2025).
Srivastava, S., Dey, S. & Mukhopadhyay, S. Vaccines against tuberculosis: where are we now? Vaccines 11, 1013 (2023).
Furin, J., Cox, H. & Pai, M. Tuberculosis. Lancet 393, 1642–1656 (2019).
Drain, P.K. et al. Incipient and subclinical tuberculosis: a clinical review of early stages and progression of infection. Clin. Microbiol. Rev. 31, e00021-18 (2018).
Goig, G. A. et al. Ecology, global diversity and evolutionary mechanisms in the Mycobacterium tuberculosis complex. Nat. Rev. Microbiol. 23, 602–614 (2025).
Ford, C. B. et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat. Genet. 45, 784–790 (2013).
Branchett, W. J. et al. Airway immune signatures of protection and disease progression in recent human tuberculosis household contacts. Nat. Immunol. https://doi.org/10.1038/s41590-026-02544-0 (2026). This study shows that in TB progression, airways dominated by neutrophils are associated with reduced, exhausted and cytotoxic T cells, whereas nonprogressor contacts retain quiescent, regulatory, stem-like T cell profiles.
Esmail, H. et al. PET-CT benchmarked detection and 5-year progression of asymptomatic tuberculosis: a longitudinal, prospective cohort study. Lancet Respir. Med. https://doi.org/10.1016/S2213-2600(26)00056-1 (2026).
Esmail, H. et al. Characterization of progressive HIV-associated tuberculosis using 2-deoxy-2-[18F]fluoro-D-glucose positron emission and computed tomography. Nat. Med. 22, 1090–1093 (2016). This study shows that PET–CT alterations precede progression to TB disease.
Esmail, H. et al. The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons. Annu. Rev. Immunol. 36, 603–638 (2018).
Wang, C. Y. An experimental study of latent tuberculosis. The Lancet 188, 417–419 (1916).
Behr, M. A., Edelstein, P. H. & Ramakrishnan, L. Rethinking the burden of latent tuberculosis to reprioritize research. Nat. Microbiol. 9, 1157–1158 (2024).
Tabone, O. et al. Blood transcriptomics reveal the evolution and resolution of the immune response in tuberculosis. J. Exp. Med. 218, e20210915 (2021). This study illustrates how the immune response changes during TB progression and resolution and how blood transcriptomics can be used to follow those changes.
Charalambous, S. et al. Contribution of reinfection to recurrent tuberculosis in South African gold miners. Int. J. Tuberc. Lung Dis. 12, 942–948 (2008).
van Helden, P. D., Warren, R. M. & Uys, P. Predicting reinfection in tuberculosis. J. Infect. Dis. 197, 172–173 (2008).
Barry, C. E. et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat. Rev. Microbiol. 7, 845–855 (2009).
Lin, P. L. & Flynn, J. L. The end of the binary era: revisiting the spectrum of tuberculosis. J. Immunol. 201, 2541–2548 (2018).
Simmons, J. D. et al. Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection. Nat. Rev. Immunol. 18, 575–589 (2018).
Coussens, A. K. et al. Classification of early tuberculosis states to guide research for improved care and prevention: an international Delphi consensus exercise. Lancet Respir. Med. 12, 484–498 (2024).
Emery, J.C. et al. Estimating the contribution of subclinical tuberculosis disease to transmission: an individual patient data analysis from prevalence surveys. eLife 12, e82469 (2023). This study is among the first studies raising the hypothesis that transmission may not require pulmonary, active TB disease.
Dinkele, R. et al. Aerosolization of Mycobacterium tuberculosis by tidal breathing. Am. J. Respir. Crit. Care Med. 206, 206–216 (2022). This study shows that viable M. tuberculosis is detected in bioaerosol samples collected during tidal breathing, independently of spontaneous cough, suggesting that transmission may occur in the absence of cough.
Patterson, B. et al. Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status. Proc. Natl Acad. Sci. USA 121, e2314813121 (2024).
Williams, C. M. et al. Exhaled Mycobacterium tuberculosis output and detection of subclinical disease by face-mask sampling: prospective observational studies. Lancet Infect. Dis. 20, 607–617 (2020).
Williams, C. M. et al. Exhaled Mycobacterium tuberculosis predicts incident infection in household contacts. Clin. Infect. Dis. 76, e957–e964 (2023).
Cadena, A. M., Fortune, S. M. & Flynn, J. L. Heterogeneity in tuberculosis. Nat. Rev. Immunol. 17, 691–702 (2017).
Scriba, T. J., Maseeme, M., Young, C., Taylor, L. & Leslie, A. J. Immunopathology in human tuberculosis. Sci. Immunol. 9, eado5951 (2024).
Sossen, B. et al. The natural history of untreated pulmonary tuberculosis in adults: a systematic review and meta-analysis. Lancet Respir. Med. 11, 367–379 (2023).
Tulu, B. et al. Host- and pathogen-related determinants of pulmonary versus extrapulmonary tuberculosis. Eur. Respir. Rev. 35, 250174 (2026).
Huynh, J. et al. Tuberculous meningitis: progress and remaining questions. Lancet Neurol. 21, 450–464 (2022).
Moule, M. G. & Cirillo, J. D. Mycobacterium tuberculosis dissemination plays a critical role in pathogenesis. Front. Cell Infect. Microbiol. 10, 65 (2020).
Wilkinson, R. J. et al. Tuberculous meningitis. Nat. Rev. Neurol. 13, 581–598 (2017).
Flynn, J. L., Gideon, H. P., Mattila, J. T. & Lin, P. L. Immunology studies in non-human primate models of tuberculosis. Immunol. Rev. 264, 60–73 (2015).
O’Garra, A. et al. The immune response in tuberculosis. Annu. Rev. Immunol. 31, 475–527 (2013).
Orme, I. M., Robinson, R. T. & Cooper, A. M. The balance between protective and pathogenic immune responses in the TB-infected lung. Nat. Immunol. 16, 57–63 (2015).
Casanova, J. L., MacMicking, J. D. & Nathan, C. F. Interferon-γ and infectious diseases: lessons and prospects. Science 384, eadl2016 (2024).
Keane, J. et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N. Engl. J. Med. 345, 1098–1104 (2001).
Mayer-Barber, K. D. & Barber, D. L. Innate and adaptive cellular immune responses to Mycobacterium tuberculosis infection. Cold Spring Harb. Perspect. Med. 5, a018424 (2015).
Silverio, D., Goncalves, R., Appelberg, R. & Saraiva, M. Advances on the role and applications of interleukin-1 in tuberculosis. mBio 12, e0313421 (2021).
Ramakrishnan, L. Revisiting the role of the granuloma in tuberculosis. Nat. Rev. Immunol. 12, 352–366 (2012).
Zhu, J., Liu, Y. J. & Fortune, S. M. Spatiotemporal perspectives on tuberculosis chemotherapy. Curr. Opin. Microbiol. 72, 102266 (2023).
Riaz, S.M. et al. Novel insights into the pathogenesis of human post-primary tuberculosis from archival material of the pre-antibiotic era, 1931–1947. Pathogens 12, 1426 (2023). This study provides insights into differences in the immunopathogenesis of primary and postprimary TB disease in humans, based on archival samples.
Boisson-Dupuis, S. et al. Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant. Sci. Immunol. 3, eaau8714 (2018).
Kerner, G. et al. Homozygosity for TYK2 P1104A underlies tuberculosis in about 1% of patients in a cohort of European ancestry. Proc. Natl Acad. Sci. USA 116, 10430–10434 (2019).
Ogishi, M. et al. Inherited human ITK deficiency impairs IFN-γ immunity and underlies tuberculosis. J. Exp. Med. 220, e20220484 (2023).
Okada, S. et al. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science 349, 606–613 (2015).
Bogunovic, D. et al. Mycobacterial disease and impaired IFN-γ immunity in humans with inherited ISG15 deficiency. Science 337, 1684–1688 (2012).
Okada, S. et al. Human STAT1 gain-of-function heterozygous mutations: chronic mucocutaneous candidiasis and type I interferonopathy. J. Clin. Immunol. 40, 1065–1081 (2020).
Ogishi, M. et al. Human LY9 governs CD4+ T cell IFN-γ immunity to Mycobacterium tuberculosis. Sci. Immunol. 10, eads7377 (2025).
Arias, A. A. et al. Tuberculosis in otherwise healthy adults with inherited TNF deficiency. Nature 633, 417–425 (2024).
Flynn, J. L. et al. Tumor necrosis factor-α is required in the protective immune response against Mycobacterium tuberculosis in mice. Immunity 2, 561–572 (1995).
Meintjes, G. & Maartens, G. HIV-associated tuberculosis. N. Engl. J. Med. 391, 343–355 (2024).
Sossen, B., Kubjane, M. & Meintjes, G. Tuberculosis and HIV coinfection: progress and challenges towards reducing incidence and mortality. Int. J. Infect. Dis. 155, 107876 (2025).
Foreman, T. W. et al. CD4+ T cells are rapidly depleted from tuberculosis granulomas following acute SIV co-infection. Cell Rep. 39, 110896 (2022).
Gupta, A., Wood, R., Kaplan, R., Bekker, L. G. & Lawn, S. D. Tuberculosis incidence rates during 8 years of follow-up of an antiretroviral treatment cohort in South Africa: comparison with rates in the community. PLoS ONE 7, e34156 (2012).
Diedrich, C. R. et al. SIV and Mycobacterium tuberculosis synergy within the granuloma accelerates the reactivation pattern of latent tuberculosis. PLoS Pathog. 16, e1008413 (2020).
Kgoadi, K. et al. Alveolar macrophages from persons with HIV mount impaired TNF signaling networks to M. tuberculosis infection. Nat. Commun. 16, 2397 (2025). Through single-cell transcriptomics on BAL cells, this study shows the effect of HIV co-infection in TB immunity in alveolar macrophage responses, beyond CD4+T cell depletion.
Correa-Macedo, W. et al. Alveolar macrophages from persons living with HIV show impaired epigenetic response to Mycobacterium tuberculosis. J. Clin. Invest. 131, e148013 (2021).
Sharan, R. et al. Antiretroviral therapy timing impacts latent tuberculosis infection reactivation in a Mycobacterium tuberculosis/SIV coinfection model. J. Clin. Invest. 132, e153090 (2022).
Marks, S. M. et al. Outcomes of contact investigations of infectious tuberculosis patients. Am. J. Respir. Crit. Care Med. 162, 2033–2038 (2000).
Gutierrez, J., Kroon, E. E., Moller, M. & Stein, C. M. Phenotype definition for ‘resisters’ to Mycobacterium tuberculosis infection in the literature—a review and recommendations. Front. Immunol. 12, 619988 (2021).
Carbone Ada, S. et al. Active and latent tuberculosis in Brazilian correctional facilities: a cross-sectional study. BMC Infect. Dis. 15, 24 (2015).
Cobat, A. et al. Tuberculin skin test reactivity is dependent on host genetic background in Colombian tuberculosis household contacts. Clin. Infect. Dis. 54, 968–971 (2012).
Cobat, A. et al. High heritability of antimycobacterial immunity in an area of hyperendemicity for tuberculosis disease. J. Infect. Dis. 201, 15–19 (2010).
Cobat, A. et al. Two loci control tuberculin skin test reactivity in an area hyperendemic for tuberculosis. J. Exp. Med. 206, 2583–2591 (2009).
Cobat, A. et al. Tuberculin skin test negativity is under tight genetic control of chromosomal region 11p14-15 in settings with different tuberculosis endemicities. J. Infect. Dis. 211, 317–321 (2015).
Simmons, J. D. et al. Monocyte metabolic transcriptional programs associate with resistance to tuberculin skin test/interferon-γ release assay conversion. J. Clin. Invest. 131, e140073 (2021).
Sun, M. et al. Specific CD4+ T cell phenotypes associate with bacterial control in people who ‘resist’ infection with Mycobacterium tuberculosis. Nat. Immunol. 25, 1411–1421 (2024). Together with Simmons et al. (2021), this study provides evidence on the immune mechanisms operating in TB resisters, reporting both innate and adaptive responses independent of IFNγ.
Proulx, M.K. et al. Noncanonical T cell responses are associated with protection from tuberculosis in mice and humans. J. Exp. Med. 222, e20241760 (2025).
Quistrebert, J. et al. Genome-wide association study of resistance to Mycobacterium tuberculosis infection identifies a locus at 10q26.2 in three distinct populations. PLoS Genet. 17, e1009392 (2021).
Cross, D. L. et al. MR1-restricted T cell clonotypes are associated with ‘resistance’ to Mycobacterium tuberculosis infection. JCI Insight 9, e166505 (2024).
Dallmann-Sauer, M. et al. Mycobacterium tuberculosis resisters despite HIV exhibit activated T cells and macrophages in their pulmonary alveoli. J. Clin. Invest. 135, e188016 (2025).
Lu, L. L. et al. IFN-γ-independent immune markers of Mycobacterium tuberculosis exposure. Nat. Med. 25, 977–987 (2019).
Foreman, T. W. et al. CD4+ T-cell-independent mechanisms suppress reactivation of latent tuberculosis in a macaque model of HIV coinfection. Proc. Natl Acad. Sci. USA 113, E5636–E5644 (2016).
Verrall, A. J. et al. Early clearance of Mycobacterium tuberculosis: the INFECT case contact cohort study in Indonesia. J. Infect. Dis. 221, 1351–1360 (2020).
Koeken, V., Verrall, A. J., Netea, M. G., Hill, P. C. & van Crevel, R. Trained innate immunity and resistance to Mycobacterium tuberculosis infection. Clin. Microbiol. Infect. 25, 1468–1472 (2019).
Cadena, A. M., Flynn, J. L. & Fortune, S. M. The importance of first impressions: early events in Mycobacterium tuberculosis infection influence outcome. mBio 7, e00342-00316 (2016).
Cohen, S. B. et al. Alveolar macrophages provide an early Mycobacterium tuberculosis niche and initiate dissemination. Cell Host Microbe 24, 439–446 (2018).
Pisu, D., Huang, L., Grenier, J. K. & Russell, D. G. Dual RNA-seq of Mtb-infected macrophages in vivo reveals ontologically distinct host–pathogen interactions. Cell Rep. 30, 335–350 (2020).
Huang, L., Nazarova, E. V., Tan, S., Liu, Y. & Russell, D. G. Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny. J. Exp. Med. 215, 1135–1152 (2018).
Pisu, D., Johnston, L., Mattila, J. T. & Russell, D. G. The frequency of CD38+ alveolar macrophages correlates with early control of M. tuberculosis in the murine lung. Nat. Commun. 15, 8522 (2024).
Pisu, D. et al. Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung. J. Exp. Med. 218, e20210615 (2021).
Zheng, W. et al. Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection. PLoS Pathog. 20, e1012205 (2024).
Scriba, T. J. et al. Sequential inflammatory processes define human progression from M. tuberculosis infection to tuberculosis disease. PLoS Pathog. 13, e1006687 (2017).
Nathan, A. et al. Multimodally profiling memory T cells from a tuberculosis cohort identifies cell state associations with demographics, environment and disease. Nat. Immunol. 22, 781–793 (2021).
Shanmugasundaram, U. et al. Pulmonary Mycobacterium tuberculosis control associates with CXCR3- and CCR6-expressing antigen-specific TH1 and TH17 cell recruitment. JCI Insight 5, e137858 (2020).
Lindestam Arlehamn, C. S. et al. Memory T cells in latent Mycobacterium tuberculosis infection are directed against three antigenic islands and largely contained in a CXCR3+CCR6+ TH1 subset. PLoS Pathog. 9, e1003130 (2013).
Gideon, H. P. et al. Multimodal profiling of lung granulomas in macaques reveals cellular correlates of tuberculosis control. Immunity 55, 827–846 (2022).
Ogongo, P. et al. Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung. J. Clin. Invest. 131, e142014 (2021).
Pollara, G. et al. Exaggerated IL-17A activity in human in vivo recall responses discriminates active tuberculosis from latent infection and cured disease. Sci. Transl. Med. 13, eabg7673 (2021).
Sallin, M. A. et al. Host resistance to pulmonary Mycobacterium tuberculosis infection requires CD153 expression. Nat. Microbiol. 3, 1198–1205 (2018).
Du Bruyn, E. et al. Mycobacterium tuberculosis-specific CD4+ T cells expressing CD153 inversely associate with bacterial load and disease severity in human tuberculosis. Mucosal Immunol. 14, 491–499 (2021).
Panda, S. et al. Identification of differentially recognized T cell epitopes in the spectrum of tuberculosis infection. Nat. Commun. 15, 765 (2024).
Sakai, S. et al. Control of Mycobacterium tuberculosis infection by a subset of lung parenchyma-homing CD4+ T cells. J. Immunol. 192, 2965–2969 (2014).
Comas, I. et al. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat. Genet. 42, 498–503 (2010).
Lefrancais, E., Hudrisier, D., Neyrolles, O., Behar, S. M. & Ernst, J. D. Finding and filling the knowledge gaps in mechanisms of T cell-mediated TB immunity to inform vaccine design. Nat. Rev. Immunol. 25, 798–815 (2025).
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).
Esaulova, E. et al. The immune landscape in tuberculosis reveals populations linked to disease and latency. Cell Host Microbe 29, 165–178 (2021).
Roy Chowdhury, R. et al. A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes. Nature 560, 644–648 (2018).
Krause, R. et al. B cell heterogeneity in human tuberculosis highlights compartment-specific phenotype and functional roles. Commun. Biol. 7, 584 (2024).
Lu, L. L. et al. A functional role for antibodies in tuberculosis. Cell 167, 433–443 (2016).
Lu, L. L. et al. Antibody Fc glycosylation discriminates between latent and active tuberculosis. J. Infect. Dis. 222, 2093–2102 (2020).
Grace, P. S. et al. Antibody-Fab and -Fc features promote Mycobacterium tuberculosis restriction. Immunity 58, 1586–1597 (2025).
Irvine, E. B. et al. Fc-engineered antibodies promote neutrophil-dependent control of Mycobacterium tuberculosis. Nat. Microbiol. 9, 2369–2382 (2024).
Bouzeyen, R. et al. Early antibody-mediated immunity to tuberculosis in mice requires NLRP3. Preprint at bioRxiv https://doi.org/10.1101/2025.07.18.665318 (2025).
Berry, M. P. et al. An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis. Nature 466, 973–977 (2010). This is an early report demonstrating a type I IFN-inducible transcriptional signature in the blood of individuals with active TB.
Singhania, A. et al. A modular transcriptional signature identifies phenotypic heterogeneity of human tuberculosis infection. Nat. Commun. 9, 2308 (2018).
Bloom, C. I. et al. Detectable changes in the blood transcriptome are present after two weeks of antituberculosis therapy. PLoS ONE 7, e46191 (2012).
Thompson, E. G. et al. Host blood RNA signatures predict the outcome of tuberculosis treatment. Tuberculosis 107, 48–58 (2017).
Mulenga, H. et al. Longitudinal dynamics of a blood transcriptomic signature of tuberculosis. Am. J. Respir. Crit. Care Med. 204, 1463–1472 (2021).
Joosten, S. A., Fletcher, H. A. & Ottenhoff, T. H. A helicopter perspective on TB biomarkers: pathway and process based analysis of gene expression data provides new insight into TB pathogenesis. PLoS ONE 8, e73230 (2013).
Maertzdorf, J. et al. Human gene expression profiles of susceptibility and resistance in tuberculosis. Genes Immun. 12, 15–22 (2011).
Lowe, D. M. et al. Neutrophilia independently predicts death in tuberculosis. Eur. Respir. J. 42, 1752–1757 (2013).
Eum, S. Y. et al. Neutrophils are the predominant infected phagocytic cells in the airways of patients with active pulmonary TB. Chest 137, 122–128 (2010).
McCaffrey, E. F. et al. The immunoregulatory landscape of human tuberculosis granulomas. Nat. Immunol. 23, 318–329 (2022).
Branchett, W. J. et al. Type I IFN drives neutrophil swarming, impeding lung T cell–macrophage interactions and TB control. J. Exp. Med. 222, e20250466 (2025).
Gern, B.H. et al. Early and opposing neutrophil and CD4+ T cell responses shape pulmonary tuberculosis pathology. J. Exp. Med. 222, e20250161 (2025). Together with Branchhett et al. (2025), this study shows how the TB lesion architecture contributes to immune networks and defines the outcome of M. tuberculosis infection of mice in vivo.
Keller, C. et al. Genetically determined susceptibility to tuberculosis in mice causally involves accelerated and enhanced recruitment of granulocytes. Infect. Immun. 74, 4295–4309 (2006).
Kimmey, J. M. et al. Unique role for ATG5 in neutrophil-mediated immunopathology during M. tuberculosis infection. Nature 528, 565–569 (2015).
Moreira-Teixeira, L. et al. Type I IFN exacerbates disease in tuberculosis-susceptible mice by inducing neutrophil-mediated lung inflammation and NETosis. Nat. Commun. 11, 5566 (2020).
Nandi, B. & Behar, S. M. Regulation of neutrophils by interferon-γ limits lung inflammation during tuberculosis infection. J. Exp. Med. 208, 2251–2262 (2011).
Ahmed, M. et al. Immune correlates of tuberculosis disease and risk translate across species. Sci. Transl. Med. 12, eaay0233 (2020).
Moreira-Teixeira, L. et al. Mouse transcriptome reveals potential signatures of protection and pathogenesis in human tuberculosis. Nat. Immunol. 21, 464–476 (2020). This study shows that the whole-blood transcriptional signature of human TB can be recapitulated in a TB-susceptible mouse model of aerosol infection.
Ji, D. X. et al. Type I interferon-driven susceptibility to Mycobacterium tuberculosis is mediated by IL-1Ra. Nat. Microbiol. 4, 2128–2135 (2019).
Kotov, D. I. et al. Early cellular mechanisms of type I interferon-driven susceptibility to tuberculosis. Cell 186, 5536–5553 (2023).
Kinsella, R. L. et al. ATG5 suppresses type I IFN-dependent neutrophil effector functions during Mycobacterium tuberculosis infection in mice. Nat. Microbiol. 10, 1323–1339 (2025).
Ong, C. W. et al. Neutrophil-derived MMP-8 drives AMPK-dependent matrix destruction in human pulmonary tuberculosis. PLoS Pathog. 11, e1004917 (2015).
Chowdhury, C. S. et al. Type I IFN-mediated NET release promotes Mycobacterium tuberculosis replication and is associated with granuloma caseation. Cell Host Microbe 32, 2092–2111 (2024).
Lee, A. M., Laurent, P., Nathan, C. F. & Barrat, F. J. Neutrophil–plasmacytoid dendritic cell interaction leads to production of type I IFN in response to Mycobacterium tuberculosis. Eur. J. Immunol. 54, e2350666 (2024).
Kauffman, K. D. et al. Defective positioning in granulomas but not lung-homing limits CD4+ T-cell interactions with Mycobacterium tuberculosis-infected macrophages in rhesus macaques. Mucosal Immunol. 11, 462–473 (2018).
Srivastava, S. & Ernst, J. D. Direct recognition of infected cells by CD4+ T cells is required for control of intracellular Mycobacterium tuberculosis in vivo. J. Immunol. 191, 1016–1020 (2013).
Lovewell, R. R., Baer, C. E., Mishra, B. B., Smith, C. M. & Sassetti, C. M. Granulocytes act as a niche for Mycobacterium tuberculosis growth. Mucosal Immunol. 14, 229–241 (2021).
Martineau, A. R. et al. Neutrophil-mediated innate immune resistance to mycobacteria. J. Clin. Invest. 117, 1988–1994 (2007).
Blomgran, R. & Ernst, J. D. Lung neutrophils facilitate activation of naive antigen-specific CD4+ T cells during Mycobacterium tuberculosis infection. J. Immunol. 186, 7110–7119 (2011).
Lee, R. S. et al. Population genomics of Mycobacterium tuberculosis in the Inuit. Proc. Natl Acad. Sci. USA 112, 13609–13614 (2015).
Bastos, H. N., Osorio, N. S., Gagneux, S., Comas, I. & Saraiva, M. The troika host–pathogen–extrinsic factors in tuberculosis: modulating inflammation and clinical outcomes. Front. Immunol. 8, 1948 (2017).
Sweeney, M. I., Carranza, C. E. & Tobin, D. M. Understanding Mycobacterium tuberculosis through its genomic diversity and evolution. PLoS Pathog. 21, e1012956 (2025).
Carmona, J. et al. Mycobacterium tuberculosis strains are differentially recognized by TLRs with an impact on the immune response. PLoS ONE 8, e67277 (2013).
Manca, C. et al. Hypervirulent M. tuberculosis W/Beijing strains upregulate type I IFNs and increase expression of negative regulators of the JAK–STAT pathway. J. Interferon Cytokine Res. 25, 694–701 (2005).
Reed, M. B. et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 431, 84–87 (2004).
Tsenova, L. et al. Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli. J. Infect. Dis. 192, 98–106 (2005).
Saelens, J. W. et al. An ancestral mycobacterial effector promotes dissemination of infection. Cell 185, 4507–4525 (2022).
Sousa, J. et al. Mycobacterium tuberculosis associated with severe tuberculosis evades cytosolic surveillance systems and modulates IL-1β production. Nat. Commun. 11, 1949 (2020).
Farzand, R. et al. A persistent tuberculosis outbreak in the UK is characterized by hydrophobic FADB4-deficient Mycobacterium tuberculosis that replicates rapidly in macrophages. mBio 13, e0265622 (2022).
Lovey, A. et al. Early alveolar macrophage response and IL-1R-dependent T cell priming determine transmissibility of Mycobacterium tuberculosis strains. Nat. Commun. 13, 884 (2022). Together with Sousa et al. (2020) and Farzand et al. (2022), these studies show that some strains of M. tuberculosis have evolved mechanisms of manipulating IL-1 responses, which affect the severity of TB and the transmissibility of the bacili.
Verma, S. et al. Transmission phenotype of Mycobacterium tuberculosis strains is mechanistically linked to induction of distinct pulmonary pathology. PLoS Pathog. 15, e1007613 (2019).
Groschel, M. I. et al. Differential rates of Mycobacterium tuberculosis transmission associate with host–pathogen sympatry. Nat. Microbiol. 9, 2113–2127 (2024).
Stanley, S. et al. Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains. Lancet Microbe 5, e570–e580 (2024).
Larsen, S. E. et al. The chosen few: Mycobacterium tuberculosis isolates for IMPAc-TB. Front. Immunol. 15, 1427510 (2024).
Caws, M. et al. The influence of host and bacterial genotype on the development of disseminated disease with Mycobacterium tuberculosis. PLoS Pathog. 4, e1000034 (2008).
McHenry, M. L. et al. Interaction between host genes and Mycobacterium tuberculosis lineage can affect tuberculosis severity: evidence for coevolution? PLoS Genet. 16, e1008728 (2020).
Phelan, J. et al. Genome-wide host–pathogen analyses reveal genetic interaction points in tuberculosis disease. Nat. Commun. 14, 549 (2023).
Xu, Z. M. et al. Genome-to-genome analysis reveals associations between human and mycobacterial genetic variation in tuberculosis patients from Tanzania. BMC Med. Genomics 18, 99 (2025).
Cohen, S. B. et al. Host and pathogen genetic diversity shape vaccine-mediated protection to Mycobacterium tuberculosis. Front. Immunol. 15, 1427846 (2024).
Smith, C. M. et al. Host–pathogen genetic interactions underlie tuberculosis susceptibility in genetically diverse mice. eLife 11, e74419 (2022).
Smith, C. M. et al. Functionally overlapping variants control tuberculosis susceptibility in collaborative cross mice. mBio 10, e02791-19 (2019).
Dinkele, R. et al. Persistent Mycobacterium tuberculosis bioaerosol release in a tuberculosis-endemic setting. iScience 27, 110731 (2024).
Acuna-Villaorduna, C. et al. Intensity of exposure to pulmonary tuberculosis determines risk of tuberculosis infection and disease. Eur. Respir. J. 51, 1701578 (2018).
Fox, G. J., Orlova, M. & Schurr, E. Tuberculosis in newborns: the lessons of the ‘Lubeck disaster’ (1929–1933). PLoS Pathog. 12, e1005271 (2016).
Tsenova, L. et al. Inoculum size and traits of the infecting clinical strain define the protection level against Mycobacterium tuberculosis infection in a rabbit model. Eur. J. Immunol. 50, 858–872 (2020).
Plumlee, C. R. et al. Ultra-low dose aerosol infection of mice with Mycobacterium tuberculosis more closely models human tuberculosis. Cell Host Microbe 29, 68–82 (2021).
van Rie, A. et al. Reinfection and mixed infection cause changing Mycobacterium tuberculosis drug-resistance patterns. Am. J. Respir. Crit. Care Med. 172, 636–642 (2005).
van Rie, A. et al. Exogenous reinfection as a cause of recurrent tuberculosis after curative treatment. N. Engl. J. Med. 341, 1174–1179 (1999).
Verver, S. et al. Rate of reinfection tuberculosis after successful treatment is higher than rate of new tuberculosis. Am. J. Respir. Crit. Care Med. 171, 1430–1435 (2005).
Moreno-Molina, M. et al. Genomic analyses of Mycobacterium tuberculosis from human lung resections reveal a high frequency of polyclonal infections. Nat. Commun. 12, 2716 (2021).
Ackley, S. F. et al. Multiple exposures, reinfection and risk of progression to active tuberculosis. R. Soc. Open Sci. 6, 180999 (2019).
Lee, R. S., Proulx, J. F., Menzies, D. & Behr, M. A. Progression to tuberculosis disease increases with multiple exposures. Eur. Respir. J. 48, 1682–1689 (2016).
Asare-Baah, M., Seraphin, M. N., Salmon, L. A. T. & Lauzardo, M. Effect of mixed strain infections on clinical and epidemiological features of tuberculosis in Florida. Infect. Genet. Evol. 87, 104659 (2021).
Shin, S. S. et al. Mixed Mycobacterium tuberculosis-strain infections are associated with poor treatment outcomes among patients with newly diagnosed tuberculosis, independent of pretreatment heteroresistance. J. Infect. Dis. 218, 1974–1982 (2018).
Allwood, B. W. et al. Post-tuberculosis lung disease: clinical review of an under-recognised global challenge. Respiration 100, 751–763 (2021).
Cadena, A. M. et al. Concurrent infection with Mycobacterium tuberculosis confers robust protection against secondary infection in macaques. PLoS Pathog. 14, e1007305 (2018).
Andrews, J. R. et al. Risk of progression to active tuberculosis following reinfection with Mycobacterium tuberculosis. Clin. Infect. Dis. 54, 784–791 (2012).
Joslyn, L. R., Flynn, J. L., Kirschner, D. E. & Linderman, J. J. Concomitant immunity to M. tuberculosis infection. Sci. Rep. 12, 20731 (2022).
Bromley, J. D. et al. CD4+ T cells re-wire granuloma cellularity and regulatory networks to promote immunomodulation following Mtb reinfection. Immunity 57, 2380–2398 (2024).
Lai, R., Ogunsola, A. F., Rakib, T. & Behar, S. M. Key advances in vaccine development for tuberculosis-success and challenges. NPJ Vaccines 8, 158 (2023).
Barber, D. L., Mayer-Barber, K. D., Feng, C. G., Sharpe, A. H. & Sher, A. CD4+ T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J. Immunol. 186, 1598–1607 (2011).
Flynn, J. L. & Chan, J. Immune cell interactions in tuberculosis. Cell 185, 4682–4702 (2022).
Ogongo, P. et al. Rare variable M. tuberculosis antigens induce predominant TH17 responses in human infection. JCI Insight. 11, e202134 (2026).
Leddy, O. et al. Immunopeptidomics can inform the design of mRNA vaccines for the delivery of Mycobacterium tuberculosis MHC class II antigens. Sci. Transl. Med. 17, eadw9184 (2025).
Leddy, O., Yuki, Y., Carrington, M., Bryson, B. D. & White, F. M. Targeting infection-specific peptides in immunopeptidomics studies for vaccine target discovery. J. Exp. Med. 222, e20250444 (2025).
Fletcher, H. A. et al. T-cell activation is an immune correlate of risk in BCG vaccinated infants. Nat. Commun. 7, 11290 (2016).
Irvine, E. B. et al. Robust IgM responses following intravenous vaccination with Bacille Calmette–Guerin associate with prevention of Mycobacterium tuberculosis infection in macaques. Nat. Immunol. 22, 1515–1523 (2021).
Smith, C. M. et al. Tuberculosis susceptibility and vaccine protection are independently controlled by host genotype. mBio 7, e01516-16 (2016).
Darrah, P. A. et al. Prevention of tuberculosis in macaques after intravenous BCG immunization. Nature 577, 95–102 (2020).
Simonson, A. W. et al. Intravenous BCG-mediated protection against tuberculosis requires CD4+ T cells and CD8α+ lymphocytes. J. Exp. Med. 222, e20241571 (2025).
Darrah, P. A. et al. Airway T cells are a correlate of i.v. Bacille Calmette–Guerin-mediated protection against tuberculosis in rhesus macaques. Cell Host Microbe 31, 962–977 (2023).
Peters, J. M. et al. High-dose intravenous BCG vaccination induces enhanced immune signaling in the airways. Sci. Adv. 11, eadq8229 (2025).
Makatsa, M. S. et al. IFN-γ−granzyme B+ natural killer cells are induced by i.v. BCG vaccination and associated with protection against tuberculosis in rhesus macaques. Mucosal Immunol. 19, 1550–1560 (2025).
Khader, S. A. et al. Targeting innate immunity for tuberculosis vaccination. J. Clin. Invest. 129, 3482–3491 (2019).
Carow, B. et al. Immune mapping of human tuberculosis and sarcoidosis lung granulomas. Front. Immunol. 14, 1332733 (2023).
Fonseca, K. L. et al. Unravelling the transcriptome of the human tuberculosis lesion and its clinical implications. Nat. Commun. 16, 5028 (2025).
Marakalala, M. J. et al. Inflammatory signaling in human tuberculosis granulomas is spatially organized. Nat. Med. 22, 531–538 (2016).
Sawyer, A. J. et al. Spatial mapping reveals granuloma diversity and histopathological superstructure in human tuberculosis. J. Exp. Med. 220, e20221392 (2023).
Gautam, U. S. et al. In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis. Proc. Natl Acad. Sci. USA 115, E62–E71 (2018).
Gregg, R. W. et al. Spatial and temporal evolution of lung granulomas in a cynomolgus macaque model of Mycobacterium tuberculosis infection. Radiol. Infect. Dis. 5, 110–117 (2018).
Seto, S. et al. Spatial multiomic profiling reveals the novel polarization of foamy macrophages within necrotic granulomatous lesions developed in lungs of C3HeB/FeJ mice infected with Mycobacterium tuberculosis. Front. Cell Infect. Microbiol. 12, 968543 (2022).
Marais, B. J., Donald, P. R., Gie, R. P., Schaaf, H. S. & Beyers, N. Diversity of disease in childhood pulmonary tuberculosis. Ann. Trop. Paediatr. 25, 79–86 (2005).
Tsukamoto, H. et al. Age-associated increase in lifespan of naive CD4+ T cells contributes to T-cell homeostasis but facilitates development of functional defects. Proc. Natl Acad. Sci. USA 106, 18333–18338 (2009).
Bozza, V. V. et al. Altered cortisol/DHEA ratio in tuberculosis patients and its relationship with abnormalities in the mycobacterial-driven cytokine production by peripheral blood mononuclear cells. Scand. J. Immunol. 66, 97–103 (2007).
Restrepo, B. I. Diabetes and tuberculosis. Microbiol. Spectr. https://doi.org/10.1128/microbiolspec.tnmi7-0023-2016 (2016).
Benmerzoug, S. et al. Sterile lung inflammation induced by silica exacerbates Mycobacterium tuberculosis infection via STING-dependent type 2 immunity. Cell Rep. 27, 2649–2664 (2019).
Ehrlich, R., Akugizibwe, P., Siegfried, N. & Rees, D. The association between silica exposure, silicosis and tuberculosis: a systematic review and meta-analysis. BMC Public Health 21, 953 (2021).
Liu, K. et al. Increased tuberculosis incidence due to immunotherapy based on PD-1 and PD-L1 blockade: a systematic review and meta-analysis. Front. Immunol. 13, 727220 (2022).
