Response to Staphylococcus aureus requires CD36-mediated phagocytosis triggered by the COOH-terminal cytoplasmic domain

Journal of Cell Biology - Tập 170 Số 3 - Trang 477-485 - 2005
Lynda M. Stuart1,2, Jiusheng Deng3, Jessica M. Silver3, Kazue Takahashi1, A. Shaw3, Elizabeth J. Hennessy1, R. Alan B. Ezekowitz1, Kathryn J. Moore3
11Laboratory of Developmental Immunology, Department of Pediatrics
23Medical Research Council Centre for Inflammation Research, University of Edinburgh, Edinburgh EH8 9AG, Scotland, UK
32Lipid Metabolism Unit, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114

Tóm tắt

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-α 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.

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Thông tin
Thông tin xuất bản

Journal of Cell Biology

Tập 170 Số 3

477-485

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