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
Published February 1, 2021
Citation Information: J Clin Invest. 2021;131(3):e136222. https://doi.org/10.1172/JCI136222.
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The knowns and unknowns of latent Mycobacterium tuberculosis infection

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 1

Evasion of T cell recognition versus T cell activation by Mtb-infected antigen-presenting cells.

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Evasion of T cell recognition versus T cell activation by Mtb-infected a...
The paradox of the T cell response to Mtb is that, on the one hand, Mtb antigens, when appropriately processed by an activated antigen-presenting cell, elicit a broad T cell response in a person with LTBI. This involves many T cell subsets responding to a wide range of antigens. These Mtb-activated T cells secrete predominantly Th1 cytokines and chemokines, possess cytotoxic T lymphocyte (CTL) function, and can provide help to B cells. On the other hand, Mtb harbored by macrophages can use a variety of mechanisms to interfere with T cell recognition. These mechanisms have primarily been identified for CD4+ T cells and include inhibition of MHC-II antigen processing, antigen escape, and inhibition of T cell receptor–CD3 signaling by Mtb glycolipids, but some may also apply to other T cell subsets. MAIT, mucosal-associated invariant T cell.