TY - JOUR
T1 - GM-CSF Dependent Differential Control of Mycobacterium tuberculosis Infection in Human and Mouse Macrophages
T2 - Is Macrophage Source of GM-CSF Critical to Tuberculosis Immunity?
AU - Mishra, Abhishek
AU - Singh, Vipul Kumar
AU - Actor, Jeffrey K.
AU - Hunter, Robert L.
AU - Jagannath, Chinnaswamy
AU - Subbian, Selvakumar
AU - Khan, Arshad
N1 - Publisher Copyright:
© Copyright © 2020 Mishra, Singh, Actor, Hunter, Jagannath, Subbian and Khan.
PY - 2020/7/23
Y1 - 2020/7/23
N2 - Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is being increasingly recognized for its potential role in innate resistance against tuberculosis (TB). While the GM-CSF is produced by a variety of host cells, including conventional and non-conventional T cells, macrophages, alveolar epithelial cells, the cell population that promotes GM-CSF mediated innate protection against Mycobacterium tuberculosis infection remains unclear. This is because studies related to the role of GM-CSF so far have been carried out in murine models of experimental TB, which is inherently susceptible to TB as compared to humans, who exhibit a resolution of infection in majority of cases. We found a significantly higher amount of GM-CSF production by human macrophages, compared to mouse macrophages, after infection with M. tuberculosis in vitro. The higher levels of GM-CSF produced by human macrophages were also directly correlated with their increased life span and ability to control M. tuberculosis infection. Other evidence from recent studies also support that M. tuberculosis infected human macrophages display heterogeneity in their antibacterial capacity, and cells with increased expression of genes involved in GM-CSF signaling pathway can control intracellular M. tuberculosis growth more efficiently. Collectively, these emerging evidence indicate that GM-CSF produced by lung resident macrophages could be vital for the host resistance against M. tuberculosis infection in humans. Identification of GM-CSF dependent key cellular pathways/processes that mediate intracellular host defense can lay the groundwork for the development of novel host directed therapies against TB as well as other intracellular infections.
AB - Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is being increasingly recognized for its potential role in innate resistance against tuberculosis (TB). While the GM-CSF is produced by a variety of host cells, including conventional and non-conventional T cells, macrophages, alveolar epithelial cells, the cell population that promotes GM-CSF mediated innate protection against Mycobacterium tuberculosis infection remains unclear. This is because studies related to the role of GM-CSF so far have been carried out in murine models of experimental TB, which is inherently susceptible to TB as compared to humans, who exhibit a resolution of infection in majority of cases. We found a significantly higher amount of GM-CSF production by human macrophages, compared to mouse macrophages, after infection with M. tuberculosis in vitro. The higher levels of GM-CSF produced by human macrophages were also directly correlated with their increased life span and ability to control M. tuberculosis infection. Other evidence from recent studies also support that M. tuberculosis infected human macrophages display heterogeneity in their antibacterial capacity, and cells with increased expression of genes involved in GM-CSF signaling pathway can control intracellular M. tuberculosis growth more efficiently. Collectively, these emerging evidence indicate that GM-CSF produced by lung resident macrophages could be vital for the host resistance against M. tuberculosis infection in humans. Identification of GM-CSF dependent key cellular pathways/processes that mediate intracellular host defense can lay the groundwork for the development of novel host directed therapies against TB as well as other intracellular infections.
KW - Mycobacterium tuberculosis
KW - cell death
KW - granulocyte monocyte colony stimulating factor
KW - innate immunity
KW - macrophage
KW - tuberculosis
UR - http://www.scopus.com/inward/record.url?scp=85089229734&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85089229734&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2020.01599
DO - 10.3389/fimmu.2020.01599
M3 - Article
C2 - 32793233
AN - SCOPUS:85089229734
VL - 11
JO - Frontiers in immunology
JF - Frontiers in immunology
SN - 1664-3224
M1 - 1599
ER -