The host immune response to Mycobacterium tuberculosis determining protection or disease progression

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).

Article  PubMed  Google Scholar 

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).

Article  CAS  PubMed  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Esmail, H. et al. The immune response to Mycobacterium tuberculosis in HIV-1-coinfected persons. Annu. Rev. Immunol. 36, 603–638 (2018).

Article  CAS  PubMed  Google Scholar 

Wang, C. Y. An experimental study of latent tuberculosis. The Lancet 188, 417–419 (1916).

Article  Google Scholar 

Behr, M. A., Edelstein, P. H. & Ramakrishnan, L. Rethinking the burden of latent tuberculosis to reprioritize research. Nat. Microbiol. 9, 1157–1158 (2024).

Article  CAS  PubMed  Google Scholar 

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).

CAS  PubMed  Google Scholar 

van Helden, P. D., Warren, R. M. & Uys, P. Predicting reinfection in tuberculosis. J. Infect. Dis. 197, 172–173 (2008).

Article  PubMed  Google Scholar 

Barry, C. E. et al. The spectrum of latent tuberculosis: rethinking the biology and intervention strategies. Nat. Rev. Microbiol. 7, 845–855 (2009).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin, P. L. & Flynn, J. L. The end of the binary era: revisiting the spectrum of tuberculosis. J. Immunol. 201, 2541–2548 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Simmons, J. D. et al. Immunological mechanisms of human resistance to persistent Mycobacterium tuberculosis infection. Nat. Rev. Immunol. 18, 575–589 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  PubMed  PubMed Central  Google Scholar 

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.

Article  PubMed  PubMed Central  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Williams, C. M. et al. Exhaled Mycobacterium tuberculosis predicts incident infection in household contacts. Clin. Infect. Dis. 76, e957–e964 (2023).

Article  PubMed  PubMed Central  Google Scholar 

Cadena, A. M., Fortune, S. M. & Flynn, J. L. Heterogeneity in tuberculosis. Nat. Rev. Immunol. 17, 691–702 (2017).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Scriba, T. J., Maseeme, M., Young, C., Taylor, L. & Leslie, A. J. Immunopathology in human tuberculosis. Sci. Immunol. 9, eado5951 (2024).

Article  CAS  PubMed  Google Scholar 

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).

Article  PubMed  Google Scholar 

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).

Article  CAS  PubMed  Google Scholar 

Moule, M. G. & Cirillo, J. D. Mycobacterium tuberculosis dissemination plays a critical role in pathogenesis. Front. Cell Infect. Microbiol. 10, 65 (2020).

Article  PubMed  PubMed Central  Google Scholar 

Wilkinson, R. J. et al. Tuberculous meningitis. Nat. Rev. Neurol. 13, 581–598 (2017).

Article  PubMed  Google Scholar 

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).

Article  CAS  PubMed  PubMed Central  Google Scholar 

O’Garra, A. et al. The immune response in tuberculosis. Annu. Rev. Immunol. 31, 475–527 (2013).

Article  PubMed  Google Scholar 

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).

Article  CAS  PubMed  Google Scholar 

Casanova, J. L., MacMicking, J. D. & Nathan, C. F. Interferon-γ and infectious diseases: lessons and prospects. Science 384, eadl2016 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Keane, J. et al. Tuberculosis associated with infliximab, a tumor necrosis factor α-neutralizing agent. N. Engl. J. Med. 345, 1098–1104 (2001).

Article  CAS  PubMed  Google Scholar 

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).

Article  PubMed  PubMed Central  Google Scholar 

Silverio, D., Goncalves, R., Appelberg, R. & Saraiva, M. Advances on the role and applications of interleukin-1 in tuberculosis. mBio 12, e0313421 (2021).

Article  PubMed  PubMed Central 

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