SLAM is a microbial sensor that regulates bacterial phagosome functions in macrophages.
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.
Berger
Scott B
SB
Division of Immunology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. sberger@bidmc.harvard.edu
Romero
Xavier
X
Ma
Chunyan
C
Wang
Guoxing
G
Faubion
William A
WA
Liao
Gongxian
G
Compeer
Ewoud
E
Keszei
Marton
M
Rameh
Lucia
L
Wang
Ninghai
N
Boes
Marianne
M
Regueiro
Jose R
JR
Reinecker
Hans-Christian
HC
Terhorst
Cox
C
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
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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