|
| Status |
Public on Oct 13, 2017 |
| Title |
Bone marrow derived macrophage vs peritoneal macrophage |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Immunometabolism is a rapidly growing field, which has led to greater understanding of innate immune cell functions. Macrophages are at the core of this research: polarized subsets of in vitro-derived cells reportedly utilize select metabolic pathways to maintain their phenotype. However, relevance of these in vitro studies to the in vivo setting is not known, and metabolic requirements are likely dependent on unique physiological and cellular metabolic environments. Here we define the metabolic requirements of peritoneal tissue-resident macrophages, the accessibility of these metabolites to cells in the peritoneum, and we dissect the role of this unique environment in maintaining a crucial macrophage function. We find that the peritoneal cavity is enriched in amino acids, most notably glutamate. Peritoneal tissue-resident macrophages have an extraordinarily large mitochondrial capacity compared with other phagocytes; this is primarily fueled by glutaminolysis, which is additionally required to maintain an extensive respiratory burst. Glutaminolysis fuels the electron transport chain, which is enhanced during tissue-resident macrophage respiratory burst via a switch to dependence of mitochondrial complex-II. This is not dependent on the level of NADPH, but requires p47 maintained NADPH-oxidase activity. Therefore, we propose that tissue-resident macrophages exploit their unique metabolic niche by implementing their glutamine-fueled mitochondrial-rich phenotype to sustain respiratory burst to assault pathogens, showing that cell-specific metabolic underpinning is important for function. Importantly, we also find that glutamine is required for the respiratory burst in human monocytes, which highlights that metabolites are not species-specific and can be the link between cellular mechanism in mouse and man.
|
| |
|
| Overall design |
M-CSF bone marrow derived macrophage (BMDM) (7 days) vs peritoneal tissue-resident macrophage, 2 vs 2 independent samples
|
| |
|
| Contributor(s) |
Davies LC, McVicar DW |
| Citation(s) |
29234000 |
| |
| Submission date |
Oct 12, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Luke Cynlais Davies |
| E-mail(s) |
luke.davies@nih.gov
|
| Organization name |
National Cancer Institute
|
| Department |
Cancer and Inflammation Program
|
| Lab |
Leukocyte Signaling Section
|
| Street address |
1050 Boyles Street
|
| City |
Frederick |
| State/province |
MARYLAND |
| ZIP/Postal code |
21702 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
|
| Samples (4)
|
| GSM2810015 |
Peritoneal tissue-resident macrophage 2 |
|
| Relations |
| BioProject |
PRJNA414129 |
| SRA |
SRP119876 |
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