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Talk by Annemarie H. Meijer

Annemarie H. Meijer, Professor of Immunobiology, Leiden University

Title: "Interplay between autophagy and cell death in mycobacterial infection"
Occasion: SFB Seminar
Host: Caroline Barisch
Start: 02.02.2023 - 16:15
Location: CellNanOs 38/201

About the speaker: Annemarie H. Meijer is a researcher in immunobiology at Leiden University, NL

Abstract of the talk: Mycobacteria are the causative agents of tuberculosis and related infections. These pathogens are able to inhibit or escape lysosomal degradation pathways, including xenophagy and LC3-associated phagocytosis. We have identified the membrane protein DRAM1, for Damage-Regulated Autophagy Modulator 1, as a key host resistance factor that augments pathogen degradation through these pathways that both rely on the autophagy machinery. With combining use of mammalian macrophages and in vivo infection in zebrafish larvae, we found that DRAM1 enhances LC3 recruitment as well as promotes the fusion of bacteria-containing vesicles with lysosomes. As a consequence, DRAM1-decifient macrophages fail to contain pathogens intracellularly and succumb to disease-exacerbating pyroptotic cell death. Interestingly, we discovered that the central mediator of pyroptosis, Gasdermin, not only permeabilizes the plasma membrane but also mediates the rupture of bacteria-containing vesicles. Thereby Gasdermin facilitates invasion of the cytosol, which renders bacteria targets for xenophagy. These results show that DRAM1 plays a central role in host resistance to intracellular infection, acting at the crossroad of autophagy and cell death, which makes it a promising target for therapeutic modulation of the microbicidal capacity of macrophages.