IRG1 Flashcards

1
Q

When is immunoresponsive gene 1 (IRG1) expressed and where?

A

IRG1 expression is rapidly induced within macrophage-lineage cells in response to live bacterial challenge and TLR agonist stimulation.

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2
Q

What is the function of immunoresponsive gene 1 (IRG1)?

A

IRG1 localises to mitochondria and functions during catabolism of the short-chain fatty acid propionate.

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3
Q

What does C/EBPB do?

A

The primary-responsive transcription factor C/EBPB helps drive infection-responsive irg1 expression within macrophage lineage-cells.

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4
Q

What is CHX and how does it affect C/EBP? Is C/EBP controlled?

A

CHX is a protein synthesis inhibition protein that enhances C/EBP expression in infected zebrafish larvae and control larvae. C/EBP is possibly controlled by a transcriptional repressor.

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5
Q

What is the effect of glucocorticoid receptor (GR) agonists on C/EBPB and IRG1?

A

Stimulation with GR agonists is sufficient to activate C/EBPB, but not IRG1.

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6
Q

How does STAT3 function in the IRG1 signalling cascade?

A

Activation of STAT3 is crucial for inducing IRG1. Inhibition of JAK/STAT signalling abolishes IRG1 expression during inflammatory responses. However, STAT3 depletion does not affect the expression of C/EBPB.

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7
Q

Which pathways regulate IRG1 expression?

A

The C/EBPB, GR, and JAK/STAT signalling pathways.

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8
Q

What happens to mitochondria that lack IRG1?

A

Mitochondria of IRG1-depleted macrophage-lineage cells are deficient in their ability to utilise fatty acids as an energy substrate for mitochondrial oxidative phosphorilation and mitochondrial ROS (mROS) production, resulting in decreased bactericidal activity.

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9
Q

Where does ROS production take place, and when?

A

ROS production is localised in the mitochondria in response to infection.

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10
Q

What is a requirement for IRG1-dependent mROS production?

A

IRG1-dependent mROS production requires fatty acid B-oxidation.

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11
Q

Which effect does IRG1-depletion have on persistence of bacterial infection?

A

IRG-depleted larvae present increased persistence of Salmonella.

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