title: Galectin-3 directs antimicrobial guanylate binding proteins to vacuoles furnished with bacterial secretion systems.
abstract: Many invasive bacteria establish pathogen-containing vacuoles (PVs) as intracellular niches for microbial growth. Immunity to these infections is dependent on the ability of host cells to recognize PVs as targets for host defense. The delivery of several host defense proteins to PVs is controlled by IFN-inducible guanylate binding proteins (GBPs), which themselves dock to PVs through poorly characterized mechanisms. Here, we demonstrate that GBPs detect the presence of bacterial protein secretion systems as "patterns of pathogenesis" associated with PVs. We report that the delivery of GBP2 toLegionella-containing vacuoles is dependent on the bacterial Dot/Icm secretion system, whereas the delivery of GBP2 toYersinia-containing vacuoles (YCVs) requires hypersecretion ofYersiniatranslocon proteins. We show that the presence of bacterial secretion systems directs cytosolic carbohydrate-binding protein Galectin-3 to PVs and that the delivery of GBP1 and GBP2 toLegionella-containing vacuoles or YCVs is substantially diminished in Galectin-3-deficient cells. Our results illustrate that insertion of bacterial secretion systems into PV membranes stimulates Galectin-3-dependent recruitment of antimicrobial GBPs to PVs as part of a coordinated host defense program.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Eric M
authors.initials: EM
authors.lastname: Feeley
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Pilla-Moffett
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Zwack
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Piro
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Ryan
authors.initials: R
authors.lastname: Finethy
authors.affiliation: Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Kolb
authors.affiliation: Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710; jorn.coers@duke.edu.|Department of Immunology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Jörn
authors.initials: J
authors.lastname: Coers
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism*; D037502:Galectin 3 / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007875:Legionella / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D000067996:RAW 264.7 Cells; D011956:Receptors, Cell Surface / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D002352:Carrier Proteins; D037502:Galectin 3; D011956:Receptors, Cell Surface; C055213:saccharide-binding proteins; D019204:GTP-Binding Proteins
keywords: galectin; guanylate binding proteins; immunity-related GTPase; interferon; ubiquitin