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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.

Original publication

DOI

10.1038/ni.1931

Type

Journal article

Journal

Nat Immunol

Publication Date

10/2010

Volume

11

Pages

920 - 927

Keywords

Animals, Antigens, CD, Apoptosis Regulatory Proteins, Bacterial Proteins, Beclin-1, Cells, Cultured, Endosomal Sorting Complexes Required for Transport, Escherichia coli, Escherichia coli Infections, Macrophages, Male, Membrane Glycoproteins, Mice, Mice, Inbred BALB C, Mice, Knockout, Molecular Chaperones, NADPH Oxidase 2, NADPH Oxidases, Phagocytosis, Phagosomes, Phosphatidylinositol 3-Kinases, Porins, Protein-Serine-Threonine Kinases, Receptors, Cell Surface, Salmonella Infections, Salmonella typhimurium, Signaling Lymphocytic Activation Molecule Family Member 1, Vacuolar Sorting Protein VPS15