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The knowns and unknowns of latent Mycobacterium tuberculosis infection
W. Henry Boom, Ulrich E. Schaible, Jacqueline M. Achkar
W. Henry Boom, Ulrich E. Schaible, Jacqueline M. Achkar
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Review

The knowns and unknowns of latent Mycobacterium tuberculosis infection

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Abstract

Humans have been infected with Mycobacterium tuberculosis (Mtb) for thousands of years. While tuberculosis (TB), one of the deadliest infectious diseases, is caused by uncontrolled Mtb infection, over 90% of presumed infected individuals remain asymptomatic and contain Mtb in a latent TB infection (LTBI) without ever developing disease, and some may clear the infection. A small number of heavily Mtb-exposed individuals appear to resist developing traditional LTBI. Because Mtb has mechanisms for intracellular survival and immune evasion, successful control involves all of the arms of the immune system. Here, we focus on immune responses to Mtb in humans and nonhuman primates and discuss new concepts and outline major knowledge gaps in our understanding of LTBI, ranging from the earliest events of exposure and infection to success or failure of Mtb control.

Authors

W. Henry Boom, Ulrich E. Schaible, Jacqueline M. Achkar

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Figure 3

Interactions between infected PMNs and macrophages can determine the balance of exacerbating versus protective host responses in LTBI.

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Interactions between infected PMNs and macrophages can determine the bal...
Wild-type but not attenuated Mtb drives PMNs into necrotic cell death in a myeloperoxidase-dependent manner. Uptake of Mtb together with necrotic PMNs by resting macrophages further promotes mycobacterial propagation and macrophage necrosis, releasing Mtb for another round of intracellular replication and macrophage death. In contrast, immune activation in LTBI equips macrophages with a potent antimicrobial armamentarium to control and possibly eliminate Mtb. MDSC, myeloid-derived suppressor cells; NET, neutrophil extracellular traps; –OCL, hypochlorite.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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