Up-regulation of human monocyte CD163 upon activation of cell-surface Toll-like receptors
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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ITGAV displayed strong co-expression with CD163.
“In the same spectrum, integrin alpha V (ITGAV) displayed strong co-expression with CD163, a well known macrophage-specific marker mediating an anti-inflammatory pathway that includes IL10, and whose synthesis was shown to be well correlated with local and systemic inflammatory phenomena [37,38].”
From Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity (2008) · cites this paper as [37]
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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
- Publisher
- Oxford University Press (OUP)
- 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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