title: SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.
abstract: Phagocytosis is a pivotal process by which macrophages eliminate microorganisms after recognition by pathogen sensors. Here we unexpectedly found that the self ligand and cell surface receptor SLAM functioned not only as a costimulatory molecule but also as a microbial sensor that controlled the killing of gram-negative bacteria by macrophages. SLAM regulated activity of the NADPH oxidase NOX2 complex and phagolysosomal maturation after entering the phagosome, following interaction with the bacterial outer membrane proteins OmpC and OmpF. SLAM recruited a complex containing the intracellular class III phosphatidylinositol kinase Vps34, its regulatory protein kinase Vps15 and the autophagy-associated molecule beclin-1 to the phagosome, which was responsible for inducing the accumulation of phosphatidylinositol-3-phosphate, a regulator of both NOX2 function and phagosomal or endosomal fusion. Thus, SLAM connects the gram-negative bacterial phagosome to ubiquitous cellular machinery responsible for the control of bacterial killing.
authors.affiliation: Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. sberger@bidmc.harvard.edu
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.forename: Xavier
authors.initials: X
authors.lastname: Romero
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.forename: Guoxing
authors.initials: G
authors.lastname: Wang
authors.forename: William A
authors.initials: WA
authors.lastname: Faubion
authors.forename: Gongxian
authors.initials: G
authors.lastname: Liao
authors.forename: Ewoud
authors.initials: E
authors.lastname: Compeer
authors.forename: Marton
authors.initials: M
authors.lastname: Keszei
authors.forename: Lucia
authors.initials: L
authors.lastname: Rameh
authors.forename: Ninghai
authors.initials: N
authors.lastname: Wang
authors.forename: Marianne
authors.initials: M
authors.lastname: Boes
authors.forename: Jose R
authors.initials: JR
authors.lastname: Regueiro
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Reinecker
authors.forename: Cox
authors.initials: C
authors.lastname: Terhorst
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics; D000071186:Beclin-1; D002478:Cells, Cultured; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000235:genetics; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D010587:Phagocytosis; D010588:Phagosomes / Q000276:immunology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D018272:Porins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D058571:Vacuolar Sorting Protein VPS15
chemical_list: D015703:Antigens, CD; D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D000071186:Beclin-1; D056827:Endosomal Sorting Complexes Required for Transport; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D019869:Phosphatidylinositol 3-Kinases; D018272:Porins; D017346:Protein Serine-Threonine Kinases; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D058571:Vacuolar Sorting Protein VPS15; C115010:Becn1 protein, mouse; C113724:OmpC protein; C109237:OmpF protein; C474475:SseB protein, Salmonella typhimurium; C488842:Cybb protein, mouse; C546852:Pik3r4 protein, mouse
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