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

Blood. 2009 Jan 22;113(4):887-92. doi: 10.1182/blood-2008-07-167064. Epub 2008 Oct 10.

Abstract

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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD / chemistry
  • Antigens, CD / genetics
  • Antigens, CD / immunology*
  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / chemistry
  • Antigens, Differentiation, Myelomonocytic / genetics
  • Antigens, Differentiation, Myelomonocytic / immunology*
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Cells, Cultured
  • Cricetinae
  • Cytokines / biosynthesis
  • Cytokines / immunology
  • Escherichia coli / immunology*
  • Humans
  • Immunity, Innate / immunology*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology*
  • Receptors, Cell Surface / metabolism
  • Receptors, Scavenger / genetics
  • Receptors, Scavenger / immunology*
  • Receptors, Scavenger / metabolism
  • Staphylococcus aureus / immunology*
  • Streptococcus mutans / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD163 antigen
  • Cytokines
  • Receptors, Cell Surface
  • Receptors, Scavenger