TY - JOUR
T1 - Macrophage heterogeneity and plasticity in tuberculosis
AU - Khan, Arshad
AU - Singh, Vipul Kumar
AU - Hunter, Robert L.
AU - Jagannath, Chinnaswamy
N1 - Publisher Copyright:
©2019 Society for Leukocyte Biology
PY - 2019/8
Y1 - 2019/8
N2 - Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status. In contrast, in a small fraction of infected individuals, the host immune response fails to control the growth of M. tuberculosis bacilli, and granulomatous TB develops progressively. Elucidating the molecular and phenotypic events that govern the outcome of the infection within macrophages is fundamental to understanding the key features of these cells that could be equally critical in infection control. The molecular details of the M. tuberculosis-macrophage interaction continue to be discerned, and emerging evidence suggests that macrophage population that participate in infection is heterogeneous. While the local environment and developmental origin could influence the phenotypic heterogeneity and functional plasticity of macrophages, M. tuberculosis has also been demonstrated to modulate the polarization of macrophages. In this review, we draw on work investigating specialized macrophage populations and their interactions with M. tuberculosis with respect to pathogenesis and specific immune responses. Understanding the mechanisms that control the repertoire of macrophage phenotypes and behaviors during infection may provide prospects for novel TB control strategies through modulation of immunobiological functions of macrophages.
AB - Macrophages are the primary host cells for Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), during its intracellular survival in humans. The pathogen has a remarkable capacity to survive within the hostile environment of macrophages. However, primary infection does not result in active TB disease in most individuals. The majority of individuals remain latently infected, wherein the bacteria are held in check by the host immune response. Nevertheless, such individuals can develop active TB later upon the decline in their immune status. In contrast, in a small fraction of infected individuals, the host immune response fails to control the growth of M. tuberculosis bacilli, and granulomatous TB develops progressively. Elucidating the molecular and phenotypic events that govern the outcome of the infection within macrophages is fundamental to understanding the key features of these cells that could be equally critical in infection control. The molecular details of the M. tuberculosis-macrophage interaction continue to be discerned, and emerging evidence suggests that macrophage population that participate in infection is heterogeneous. While the local environment and developmental origin could influence the phenotypic heterogeneity and functional plasticity of macrophages, M. tuberculosis has also been demonstrated to modulate the polarization of macrophages. In this review, we draw on work investigating specialized macrophage populations and their interactions with M. tuberculosis with respect to pathogenesis and specific immune responses. Understanding the mechanisms that control the repertoire of macrophage phenotypes and behaviors during infection may provide prospects for novel TB control strategies through modulation of immunobiological functions of macrophages.
KW - M1 M2 macrophage phenotype
KW - Mycobacterium tuberculosis, macrophages
KW - alveolar macrophages
KW - granuloma
KW - polarization
KW - tuberculosis
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U2 - 10.1002/JLB.MR0318-095RR
DO - 10.1002/JLB.MR0318-095RR
M3 - Review article
C2 - 30938876
AN - SCOPUS:85063771219
SN - 0741-5400
VL - 106
SP - 275
EP - 282
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
IS - 2
ER -