Journal of Leukocyte Biology BioLegend: Treg, Th17, Stem Cell
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Originally published online as doi:10.1189/jlb.0706428 on December 12, 2006

Published online before print December 12, 2006
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(Journal of Leukocyte Biology. 2007;81:663-671.)
© 2007 by Society for Leukocyte Biology

Up-regulation of human monocyte CD163 upon activation of cell-surface Toll-like receptors

Lehn K. Weaver*,1, Patricia A. Pioli{dagger}, Kathleen Wardwell{dagger}, Stefanie N. Vogel{ddagger} and Paul M. Guyre*,{dagger}

Departments of
* Microbiology and Immunology and
{dagger} Physiology, Dartmouth Medical School, Hanover, New Hampshire, USA; and
{ddagger} Department of Microbiology and Immunology, University of Maryland, Baltimore, Maryland, USA

1 Correspondence: Department of Microbiology and Immunology, Dartmouth Medical School, HB7700, 1 Medical Center Drive, Lebanon, NH 03756, USA. E-mail: lehn{at}dartmouth.edu

The hemoglobin (Hb) scavenger receptor, CD163, is a cell-surface glycoprotein that is expressed exclusively on monocytes and macrophages. It binds and internalizes haptoglobin-Hb complexes and has been implicated in the resolution of inflammation. Furthermore, the regulation of CD163 during an innate immune response implies an important role for this molecule in the host defense against infection. LPS, derived from the outer membrane of Gram-negative bacteria, activates TLR4 to cause acute shedding of CD163 from human monocytes, followed by recovery and induction of surface CD163 to higher levels than observed on untreated monocytes. We now report that the TLR2 and TLR5 agonists—Pam3Cys and bacterial flagellin—have similar effects on CD163 surface expression. Up-regulation of CD163 following treatment of human PBMC with TLR2, TLR4, and TLR5 agonists parallels increased production of IL-6 and IL-10, and neutralization of IL-6 and/or IL-10 blocks CD163 up-regulation. Furthermore, simultaneous stimulation of TLR2 or TLR5 in combination with TLR4 activation results in enhanced up-regulation of CD163. It is notable that exogenous recombinant IFN-{gamma} (rIFN-{gamma}) suppresses cell-surface, TLR-mediated IL-10 production as well as CD163 up-regulation. Sustained down-regulation of CD163 mediated by rIFN-{gamma} can be partially rescued with exogenous rIL-10 but not with exogenous rIL-6. This divergent regulation of CD163 by cytokines demonstrates that human monocytes react differently to infectious signals depending on the cytokine milieu they encounter. Thus, surface CD163 expression on mononuclear phagocytes is a carefully regulated component of the innate immune response to infection.

Key Words: macrophage • inflammation • innate immunity • pattern recognition receptors




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