The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/2000/1/147/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 1, January 3, 2000 147-156


Original Article

Protection from Lethal Gram-positive Infection by Macrophage Scavenger Receptor–dependent Phagocytosis

Christian A. Thomasa,b, Yongmei Lib, Tatsuhiko Kodamac, Hiroshi Suzukic, Samuel C. Silversteina,b, and Joseph El Khouryb,d
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

Correspondence to: Christian A. Thomas, Vermont Center for Cancer Medicine, 125 College Pkwy., Suite 202, Colchester, VT 05446. Tel:802-655-3400 Fax:802-655-9170 E-mail: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


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