Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain.
Phagocyte recognition and clearance of bacteria play essential roles in the host response to infection. In an on-going forward genetic screen, we identify the Drosophila melanogaster scavenger receptor Croquemort as a receptor for Staphylococcus aureus, implicating for the first time the CD36 family as phagocytic receptors for bacteria. In transfection assays, the mammalian Croquemort paralogue CD36 confers binding and internalization of Gram-positive and, to a lesser extent, Gram-negative bacteria. By mutational analysis, we show that internalization of S. aureus and its component lipoteichoic acid requires the COOH-terminal cytoplasmic portion of CD36, specifically Y463 and C464, which activates Toll-like receptor (TLR) 2/6 signaling. Macrophages lacking CD36 demonstrate reduced internalization of S. aureus and its component lipoteichoic acid, accompanied by a marked defect in tumor necrosis factor-alpha and IL-12 production. As a result, Cd36-/- mice fail to efficiently clear S. aureus in vivo resulting in profound bacteraemia. Thus, response to S. aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain, which initiates TLR2/6 signaling.
Stuart
Lynda M
LM
Laboratory of Developmental Immunology, Department of Pediatrics, Harvard Medical School, Boston, MA 02114, USA.
Deng
Jiusheng
J
Silver
Jessica M
JM
Takahashi
Kazue
K
Tseng
Anita A
AA
Hennessy
Elizabeth J
EJ
Ezekowitz
R Alan B
RA
Moore
Kathryn J
KJ
D000818:Animals; D016470:Bacteremia / Q000276:immunology / Q000382:microbiology; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000382:microbiology; D008562:Membrane Glycoproteins / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D010587:Phagocytosis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000502:physiology; D011971:Receptors, Immunologic / Q000235:genetics; D051116:Receptors, Scavenger; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000502:physiology*; D013682:Teichoic Acids / Q000378:metabolism; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D018955:CD36 Antigens; D029721:Drosophila Proteins; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C099526:crq protein, Drosophila; D018664:Interleukin-12; C009900:lipoteichoic acid