Cited by 133Immune Response and InflammationPhagocytosis and Immune RegulationImmune cells in cancer

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

Weaver, Lehn K, Pioli, Patricia A, Wardwell, Kathleen, Vogel, Stefanie N, Guyre, Paul M·2007·Journal of Leukocyte Biology

Abstract

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-γ (rIFN-γ) suppresses cell-surface, TLR-mediated IL-10 production as well as CD163 up-regulation. Sustained down-regulation of CD163 mediated by rIFN-γ 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.

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Crossref · 10.1189/jlb.0706428

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Authors
Weaver, L. K., Pioli, P. A., Wardwell, K., Vogel, S. N., & Guyre, P. M.
Affiliations
  • Dartmouth College (US)
  • University of Maryland, Baltimore (US)
Corresponding author
Weaver, Lehn K
Venue
Journal of Leukocyte Biology
Published
2006-12-12
Volume
81
Issue
3
Pages
663-671
ISSN
  • 0741-5400 (ISSN-L)
  • 1938-3673
OpenAlex
W2099734262
Cited by
133
References
39
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 9 · 2022: 10 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 4 · 2015: 4 · 2014: 7 · 2013: 8 · 2012: 15
FWCI
2.14
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Leukocyte Biology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Englert Cell Analysis Laboratory (CA23108)
  • Rippel Foundation and a National Cancer Institute Cancer Center
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Keywords
CD163, monocytes, Toll-like receptors, TLR2, TLR4, TLR5, lipopolysaccharide, Pam3Cys, flagellin, interleukin-6, IL-10, interferon-gamma, innate immune response, inflammation resolution
MeSH terms
Interleukin-6 Inhibitors, CD163 Antigen, Antibodies, Cells, Cultured, Humans, Interferon-gamma, Leukocytes, Mononuclear, Lipopolysaccharides, Polymyxin B, Receptors, Cell Surface, Recombinant Proteins, Structure-Activity Relationship, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Interleukin-6, Up-Regulation, Interleukin-10, Toll-Like Receptors

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