Comment | Published:

Are tolerance and training required to end TB?

Host defence strategies against Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), include host resistance and disease tolerance. To date, most studies have focused on resistance mechanisms, but developing new strategies to eradicate Mtb will require an understanding of the entire landscape of immunity in TB. Here I discuss two evolutionarily conserved host defence strategies, disease tolerance and trained immunity (memory-like innate immune responses), and their role in Mtb infection.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Netea, M. G. et al. Trained immunity: a program of innate immune memory in health and disease. Science 352, aaf1098 (2016).

  2. 2.

    Pai, M. et al. Tuberculosis. Nat. Rev. Dis. Primers 2, 16076 (2016).

  3. 3.

    Nunes-Alves, C. et al. In search of a new paradigm for protective immunity to TB. Nat. Rev. Microbiol. 12, 289–299 (2014).

  4. 4.

    Mishra, B. B. et al. Nitric oxide prevents a pathogen-permissive granulocytic inflammation during tuberculosis. Nat. Microbiol. 2, 17072 (2017).

  5. 5.

    Gieseck, R. L. 3rd, Wilson, M. S. & Wynn, T. A. Type 2 immunity in tissue repair and fibrosis. Nat. Rev. Immunol. 18, 62–76 (2018).

  6. 6.

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

  7. 7.

    Nemes, E. et al. Prevention of M. tuberculosis infection with H4:IC31 vaccine or BCG revaccination. N. Engl. J. Med. 379, 138–149 (2018).

  8. 8.

    Tzelepis, F. et al. Mitochondrial cyclophilin D regulates T cell metabolic responses and disease tolerance to tuberculosis. Sci. Immunol. 3, eaar4135 (2018).

  9. 9.

    Kaufmann, E. et al. BCG educates hematopoietic stem cells to generate protective innate immunity against tuberculosis. Cell 172, 176–190 (2018).

  10. 10.

    Fleming-Davies, A. E. et al. Incomplete host immunity favors the evolution of virulence in an emergent pathogen. Science 359, 1030–1033 (2018).

Download references

Acknowledgements

This work was supported by the Canadian Institute of Health Research (CIHR) Foundation Grant (FDN-143273) to M.D. and M.D. holds a Fonds de la Recherche du Quebec- Sante (FRQS) Award and the Strauss Chair in Respiratory Diseases.

Author information

Competing interests

The author declares no competing interests.

Correspondence to Maziar Divangahi.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Further reading

Fig. 1: Nuts and bolts of trained immunity.