Immunometabolism

Question 1

Name 3x metabolic properties of M1 macrophage and explain how they support inflammatory responses.

Answer 1

Pro-inflammatory (m1=inflammatory)

Bacterial killing
Kill tumor cells
Host defense
Anabolic > start making things, for example fatty acids
Short-lived
Fast ATP
Supports proliferation
Supports nitric oxide production

Support inflammatory responses:
Inflammatory cytokines

The TCA cycle and mitochondria of M1 macrophages are repurposed to support inflammation

Question 2

What is the effect of itaconate on inflammatory macrophage responses, and how is this effect mediated?

Answer 2

Itaconate = anti-inflammatory

Question 3

Name 3x metabolic properties of M2 macrophage and explain how they support pro-inflammatory responses.

Answer 3

Homeostasis
Anti-inflammatory (2words, M2)
Tissue repair
Wound healing
Promote tumor growth

High OXPHOS
Sustained ATP
Long-lived

Question 4

What does GAPDH do?

Answer 4

Regulation of macrophage activation

GAPDH can be quite heavily regulated by inflammatory stimuli

GAPDH regulates the production of inflammatory cytokines

Question 5

GAPDH in a resting macrophage?

Answer 5

Low glycolysis
Low cytokines (TNFa and IL-1B)
GAPDH gets ‘bored’ > it starts binding mRNAs of different cytokines including TNF > blocks translation of TNF

Question 6

GAPDH in an activated macrophage?

Answer 6

Cell gets activated for example with LPS > post translational modification of GAPDH > malonylation
High glycolysis
High TNFa and IL-1B
Makes GAPDH dissociate from mRNAs and starts doing function as glycolytic enzyme > helps convert glucose in pyruvate > induces glycolysis
Can indirectly effect mRNA of TNF > translation of TNF probably
GAPDH regulates the production of inflammatory cytokines