title: Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion.
abstract: 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.
authors.affiliation: MRC Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Hills Road, Cambridge CB2 0QH, UK.
authors.forename: Teresa L M
authors.initials: TL
authors.lastname: Thurston
authors.forename: Michal P
authors.initials: MP
authors.lastname: Wandel
authors.forename: Natalia
authors.initials: N
authors.lastname: von Muhlinen
authors.forename: Agnes
authors.initials: A
authors.lastname: Foeglein
authors.forename: Felix
authors.initials: F
authors.lastname: Randow
mesh_terms: D001343:Autophagy; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism / Q000382:microbiology; D022162:Cytoplasmic Vesicles / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology*; D011992:Endosomes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D037161:Galectins / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D012480:Salmonella Infections / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D012486:Salmonella typhimurium / Q000166:cytology / Q000502:physiology*
chemical_list: C094297:CALCOCO2 protein, human; D037161:Galectins; C091991:LGALS8 protein, human; D009687:Nuclear Proteins