Immunometabolism Flashcards
What is the phenotype of M1 macrophages?
M1 macrophages are pro-inflammatory and kill tumor cells and bacteria.
What is the phenotype of M2 macrophages?
M2 macrophages are anti-inflammatory and are responsible for tissue repair and wound healing.
What is the difference in ATP production between M1 and M2 macrophages?
M1 macrophages need quick ATP so use glycolysis and the pentose phosphate pathway (PPP). M2 macrophages have high oxidative phosphorylation which will result in sustained ATP.
What is a byproduct of the PPP pathway which is usefull for M1 macrophages?
In the PPP pathway M1 macrophages can generate the amino acids to make DNA for e.g. replication, and also generate ROS.
What is a byproduct of glycolysis which is usefull for M1 macrophages?
It provides building blocks to do biosynthesis (anabolism).
How can you discriminate between M1 and M2 marophage activation in terms of metabolism?
By measuring arginine converted into ornithine, because there are high amounts of arginase in M2 macrophages.
What is the metabolism of inflammatory cells?
Inflammatory cells are anabolic and synthesize fatty acids in glycolysis (biosynthesis).
What is the metabolism of tolerogenic cells?
Tolerogenic cells are catabolic and do much oxidative phosphorylation so they live long, which is good in chronic inflammation but not in tumors.
What are the functions of pyruvate (metabolic enzyme)?
It makes ATP, generates building blocks for biosynthesis and activates macrophages.
Why is GAPDH not good as housekeeping control?
GAPDH can be heavily regulated by inflammatory pathways (by for example pyruvate).
What does GAPDH do in M2 macropages?
Resting M2 don’t use a lot of glycolysis and they also don’t produce a lot of cytokines. Here GAPDH, instead of being involved in glycolysis, binds mRNA of different cytokines such as TNF so it prevents its production; it prevents inflammatory cytokine production.
How does Succinate regulate immune responses in M1 macrophages?
It can stabilize HIF1a by succinylation, which regulates hypoxia and inflammatory responses. It can also stabilize Succinate Dehydrogenase (SDH) which will generate ROS. So Succinate is pro-inflammatory.
How does Itaconate regulate immune responses?
Itaconate supresses SDH but also alkylation of KEP1, which is a suppressor of Nrf2, so Nrf2 gets activated which is anti-inflammatory. Itaconate can also supress glycolysis and it can also supress NLRP3 inflammasome.
