Insights into protection against Mycobacterium tuberculosis infection: time to officially confirm another phenotype?
Todia P. Setiabudiawan, … , Andrew R. DiNardo, Reinout van Crevel
Todia P. Setiabudiawan, … , Andrew R. DiNardo, Reinout van Crevel
Published April 1, 2025
Citation Information: J Clin Invest. 2025;135(7):e191423. https://doi.org/10.1172/JCI191423.
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Commentary

Insights into protection against Mycobacterium tuberculosis infection: time to officially confirm another phenotype?

Abstract

Immune correlates of protection against infection with Mycobacterium tuberculosis (Mtb) remain elusive. In this issue of the JCI, Dallmann-Sauer and authors demonstrate that lack of tuberculin skin test (TST) and interferon γ release assay (IGRA) conversion among people with HIV despite years-long Mtb exposure is associated with alveolar lymphocytosis, including specific poly-cytotoxic T cells, and M1-type alveolar macrophages with a stronger ex vivo response to the pathogen. Studies in these rare individuals, termed “TB resisters” and in tuberculosis household contacts who are repeatedly IGRA negative in the months after a specific exposure event (known as “early clearers”) help elucidate manipulatable mechanisms to boost protection against Mtb infection.

Authors

Todia P. Setiabudiawan, Philip C. Hill, Andrew R. DiNardo, Reinout van Crevel

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Figure 1

Different stages after exposure to Mtb.

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Different stages after exposure to Mtb. The TB resister phenotype is cha...
The TB resister phenotype is characterized by persistently negative IGRA/TST despite years-long exposure whereas early clearance reflects repeatedly negative IGRA results over a short period (e.g., 3 months) in the context of a well-defined exposure of TB household contacts to an index patient with a known Mtb isolate.