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 Blood, 22 January 2009, Vol. 113, No. 4, pp. 887-892.
Prepublished online as a Blood First Edition Paper on October 10, 2008; DOI 10.1182/blood-2008-07-167064.

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PHAGOCYTES, GRANULOCYTES, AND MYELOPOIESIS

The macrophage scavenger receptor CD163 functions as an innate immune sensor for bacteria

Babs O. Fabriek1, Robin van Bruggen2, Dong Mei Deng3, Antoon J. M. Ligtenberg4, Kamran Nazmi4, Karin Schornagel1,2, Rianka P. M. Vloet1, Christine D. Dijkstra1, and Timo K. van den Berg1,2

1 Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam; 2 Sanquin Research and Landsteiner Laboratory, Academic Medical Center, Amsterdam; and 3 Departments of Cardiology, Endodontology, Pedodontology and 4 Dental Basic Sciences, Academic Centre for Dentistry, Amsterdam, The Netherlands

The plasma membrane glycoprotein receptor CD163 is a member of the scavenger receptor cystein-rich (SRCR) superfamily class B that is highly expressed on resident tissue macrophages in vivo. Previously, the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes and to mediate cell-cell interactions between macrophages and developing erythroblasts in erythroblastic islands. Here, we provide evidence for a potential role for CD163 in host defense. In particular, we demonstrate that CD163 can function as a macrophage receptor for bacteria. CD163 was shown to bind both Gram-positive and -negative bacteria, and a previously identified cell-binding motif in the second scavenger domain of CD163 was sufficient to mediate this binding. Expression of CD163 in monocytic cells promoted bacteria-induced proinflammatory cytokine production. Finally, newly generated antagonistic antibodies against CD163 were able to potently inhibit cytokine production elicited by bacteria in freshly isolated human monocytes. These findings identify CD163 as a macrophage receptor for bacteria and suggest that, during bacterial infection, CD163 on resident tissue macrophages acts as an innate immune sensor and inducer of local inflammation.


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