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Original Article

^a Department of Medicine, Division of Medical Oncology, Columbia Presbyterian Medical Center, New York, New York 10032
^b Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032
^c Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Meguro Tokyo 153, Japan
^d Department of Medicine, Beth Israel Hospital, Albert Einstein College of Medicine, New York, New York 10003
Vermont Center for Cancer Medicine, 125 College Pkwy., Suite 202, Colchester, VT 05446.802-655-9170802-655-3400

christian.thomas{at}vetmednet.org

Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II–deficient mice (MSR-A^–/–) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A^+/+ control mice. MSR-A^–/– mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A^–/– macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II–dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.

Key Words: scavenger receptor • macrophage • phagocytosis • gram-positive bacteria • Staphylococcus aureus

Abbreviations used in this paper: LTA, lipoteichoic acid; MSR-A^–/– mice, macrophage scavenger receptor–deficient mice; MSR-A^+/+ mice, wild-type mice; SR-AI/II, type I and/or II class A macrophage scavenger receptors; TM, thioglycollate broth–elicited peritoneal macrophage(s).

J. El Khoury's present address is Infectious Disease Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St., Boston, MA 02129.

© 2000 The Rockefeller University Press

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This article has been cited by other articles:

• Lauvau, G., Pamer, E. G. (2001). Cd8 T Cell Detection of Bacterial Infection: Sniffing for Formyl Peptides Derived from Mycobacterium tuberculosis. JEM 193: f35-f40 [Full Text]  

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