TY - JOUR
T1 - Latent tuberculosis infection
T2 - Myths, models, and molecular mechanisms
AU - Dutta, Noton K.
AU - Karakousis, Petros C.
N1 - Publisher Copyright:
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PY - 2014/9/1
Y1 - 2014/9/1
N2 - The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including "latency," "persistence," "dormancy," and "antibiotic tolerance." Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, "dormant" bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI.
AB - The aim of this review is to present the current state of knowledge on human latent tuberculosis infection (LTBI) based on clinical studies and observations, as well as experimental in vitro and animal models. Several key terms are defined, including "latency," "persistence," "dormancy," and "antibiotic tolerance." Dogmas prevalent in the field are critically examined based on available clinical and experimental data, including the long-held beliefs that infection is either latent or active, that LTBI represents a small population of nonreplicating, "dormant" bacilli, and that caseous granulomas are the haven for LTBI. The role of host factors, such as CD4+ and CD8+ T cells, T regulatory cells, tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ), in controlling TB infection is discussed. We also highlight microbial regulatory and metabolic pathways implicated in bacillary growth restriction and antibiotic tolerance under various physiologically relevant conditions. Finally, we pose several clinically important questions, which remain unanswered and will serve to stimulate future research on LTBI.
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U2 - 10.1128/MMBR.00010-14
DO - 10.1128/MMBR.00010-14
M3 - Review article
C2 - 25184558
AN - SCOPUS:84907199166
SN - 1092-2172
VL - 78
SP - 343
EP - 371
JO - Microbiology and Molecular Biology Reviews
JF - Microbiology and Molecular Biology Reviews
IS - 3
ER -