Growth of Mycobacterium tuberculosis in vivo segregates with host macrophage metabolism and ontogeny

To understand how infection by (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluo...

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Bibliographic Details
Published in:The Journal of experimental medicine Vol. 215; no. 4; p. 1135
Main Authors: Huang, Lu, Nazarova, Evgeniya V, Tan, Shumin, Liu, Yancheng, Russell, David G
Format: Journal Article
Language:English
Published: United States 02.04.2018
Subjects:
Animals
Bystander Effect
Cell Cycle
Cell Proliferation
Cellular Reprogramming
Fatty Acids - metabolism
Genes, Reporter
Glycolysis
Host-Pathogen Interactions
Macrophages, Alveolar - metabolism
Macrophages, Alveolar - microbiology
Macrophages, Alveolar - pathology
Metabolic Networks and Pathways
Mice, Inbred C57BL
Models, Biological
Monocytes - pathology
Mycobacterium tuberculosis - growth & development
Oxidation-Reduction
Phagocytes - metabolism
Transcription, Genetic
Tuberculosis - microbiology
Tuberculosis - pathology
ISSN:1540-9538, 1540-9538
Online Access:Get more information
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Summary:To understand how infection by (Mtb) is modulated by host cell phenotype, we characterized those host phagocytes that controlled or supported bacterial growth during early infection, focusing on the ontologically distinct alveolar macrophage (AM) and interstitial macrophage (IM) lineages. Using fluorescent Mtb reporter strains, we found that bacilli in AM exhibited lower stress and higher bacterial replication than those in IM. Interestingly, depletion of AM reduced bacterial burden, whereas depletion of IM increased bacterial burden. Transcriptomic analysis revealed that IMs were glycolytically active, whereas AMs were committed to fatty acid oxidation. Intoxication of infected mice with the glycolytic inhibitor, 2-deoxyglucose, decreased the number of IMs yet increased the bacterial burden in the lung. Furthermore, in in vitro macrophage infections, 2-deoxyglucose treatment increased bacterial growth, whereas the fatty acid oxidation inhibitor etomoxir constrained bacterial growth. We hypothesize that different macrophage lineages respond divergently to Mtb infection, with IMs exhibiting nutritional restriction and controlling bacterial growth and AMs representing a more nutritionally permissive environment.
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ISSN:1540-9538
1540-9538
DOI:10.1084/jem.20172020