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Uncoupling of IL-6 signaling and LC3-associated phagocytosis (LAP) drives immunoparalysis during sepsis

ABSTRACT: Uncoupling of IL-6 signaling and LC3-associated phagocytosis (LAP) drives immunoparalysis during sepsis

PROVIDER: PRJNA728689 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14481400.fastq.gz	Fastqsanger.gz
	SRR14481500.fastq.gz	Fastqsanger.gz
	SRR14481401.fastq.gz	Fastqsanger.gz
	SRR14481501.fastq.gz	Fastqsanger.gz
	SRR14481402.fastq.gz	Fastqsanger.gz

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Uncoupling of IL-6 signaling and LC3-associated phagocytosis (LAP) drives immunoparalysis during sepsis

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Project description:LC3-associated phagocytosis (LAP) represents a non-canonical function of autophagy proteins in which ATG8 family proteins (LC3 and GABARAP proteins) are lipidated onto single-membrane phagosomes as particles are engulfed by phagocytic cells. LAP plays roles in innate immunity, inflammation and anti-cancer responses and is initiated upon phagocytosis of particles that stimulate Toll-like receptors (TLR), Fc-receptors, and upon engulfment of dying cells. However, how this molecular process is initiated remains elusive. Here we report that receptors that engage LAP enrich phosphatidylserine (PS) in the phagosome membrane via membrane-proximal domains that are necessary and sufficient for LAP to proceed. Subsequently, PS recruits the Rubicon-containing PI3-kinase complex to initiate the enzymatic cascade leading to LAP. Manipulation of plasma membrane PS content, PS-binding by Rubicon, or the PS-clustering domains of receptors prevents LAP and phagosome maturation. Therefore, the initiation of LAP represents a novel mechanism of PS-mediated signal transduction upon ligation of surface receptors.

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