Galectin-8 targets damaged vesicles for autophagy to defend cells against bacterial invasion

By Teresa L. M. Thurston, M. Wandel, Natalia von Muhlinen, Ágnes Foeglein, F. Randow. Nature, 2012

983 citations recorded by the source corpus.

Autophagy defends the mammalian cytosol against bacterial infection. Efficient pathogen engulfment is mediated by cargo-selecting autophagy adaptors that rely on unidentified pattern-recognition or danger receptors to label invading pathogens as autophagy cargo, typically by polyubiquitin coating. Here we show in human cells that galectin 8 (also known as LGALS8), a cytosolic lectin, is a danger receptor that restricts Salmonella proliferation. Galectin 8 monitors endosomal and lysosomal integrity and detects bacterial invasion by binding host glycans exposed on damaged Salmonella-containing vacuoles. By recruiting NDP52 (also known as CALCOCO2), galectin 8 activates antibacterial autophagy. Galectin-8-dependent recruitment of NDP52 to Salmonella-containing vesicles is transient and followed by ubiquitin-dependent NDP52 recruitment. Because galectin 8 also detects sterile damage to endosomes or lysosomes, as well as invasion by Listeria or Shigella, we suggest that galectin 8 serves as a versatile receptor for vesicle-damaging pathogens. Our results illustrate how cells deploy the danger receptor galectin 8 to combat infection by monitoring endosomal and lysosomal integrity on the basis of the specific lack of complex carbohydrates in the cytosol.

Subfields: Epidemiology, Immunology, Parasitology

View Paper: https://www.semanticscholar.org/paper/c19f15791160e1a0590c061fbba39df8c5f278d7

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Citations in the corpus

Lysosomal membrane permeabilization and cell death (2018, background): “Some galectins can directly recruit components of the autophagy machinery to initiate autophagy.(45,46) Moreover, damaged lysosomes”
Autophagy during viral infection — a double-edged sword (2018, background): “Autophagy can target invading pathogens in a process termed lC3-associated phagocytosis (lAP), which describes the recruitment of lC3 to phagosomes.”
Phagocytosis: An Immunobiologic Process. (2016, background): “Sensing of disrupted integrity of intracellular membranes by a cytoplasmic lectin, galectin 8 (e.g., after Salmonella infection), targets damaged vesicles with host ligands exposed on damaged vacuoles for autophagy, defending cells against bacterial invasion (Thurston et al., 2012).”
Molecular definitions of autophagy and related processes (2017, positive): “In mammalian cells, cytoplasmic bacteria are rapidly recognized by various autophagy receptors including p62, OPTN, NDP52, and Tax1-binding protein 1 (TAX1BP1), via a mechanism that relies on receptor phosphorylation by TANK1-binding kinase 1 (TBK1) (Thurston et al , 2009; Wild et al , 2011; Tumbare”
Extracellular M. tuberculosis DNA Targets Bacteria for Autophagy by Activating the Host DNA-Sensing Pathway (2012, positive): “In addition to detection of microbial products, cells are also able to target autophagy to intracellular pathogens by directly detecting membrane permeabilization (Thurston et al., 2012).”
Ubiquitination and selective autophagy (2012, background): “surface of Salmonella are targeted by galectin 8, a cytosolic lectin, which directly binds NDP52 promoting antibacterial autophagy in a ubiquitin-independent way.(95) This interaction is transient and followed by a ubiquitin-dependent NDP52”
The LIR motif – crucial for selective autophagy (2013, background): “In this way, cytosolic galectin-8 functions as an ubiquitinindependent ‘danger’ receptor and ‘eat-me’ signal (Thurston et al., 2012).”
Autophagy in inflammation, infection, and immunometabolism (2021, background): “, 2009), xenophagy (Ponpuak et al., 2010; Ravenhill et al., 2019; Thurston et al., 2012; Wild et al., 2011) and mitophagy (removing sources of mitoDNA and ROS that act as DAMPs) (Lazarou et al.”
Interactions between autophagy receptors and ubiquitin-like proteins form the molecular basis for selective autophagy. (2014, background): “Genetic analysis demonstrated dependence of pexophagy on the core Atg genes but also identified unique components (Till et al., 2012).”