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Updated: Apr 11, 2026
A Simple and Efficient Method for Testing Immunomodulatory Agents for Generation of Tolerogenic Dendritic Cells from Human CD14+ Monocytes
Published on: April 11, 2025
Soluble CD14 is a nonspecific marker of monocyte activation
Carey L Shive1, Wei Jiang, Donald D Anthony
1aCenter for AIDS Research, Case Western Reserve University School of Medicine, Cleveland, Ohio bDepartment of Microbiology and Immunology, Division of Infectious Diseases, Medical University of South Carolina, Charleston, South Carolina cVeterans Administration Medical Center, Cleveland, Ohio, USA.
Abstract:
Soluble CD14 is associated with morbidity and mortality in HIV disease. It is a co-receptor for lipopolysaccharide (LPS) that is released from monocytes upon activation. We demonstrate here, that inflammatory cytokines can induce the release of sCD14 in peripheral blood mononuclear cell cultures from healthy donors, and that TLR ligands other than LPS can cause a decrease in the monocyte cell surface expression of CD14. Thus, sCD14 is a marker of monocyte activation, not restricted to activation by LPS.
Insights
Soluble CD14 (sCD14), a marker linked to HIV disease outcomes, is released by monocytes activated by inflammatory cytokines. This finding indicates sCD14 reflects broader monocyte activation beyond lipopolysaccharide (LPS) exposure.
Area of Science:
- Immunology
- Cell Biology
- Infectious Disease
Background:
- Soluble CD14 (sCD14) is a known biomarker associated with increased morbidity and mortality in Human Immunodeficiency Virus (HIV) infection.
- CD14 functions as a co-receptor for lipopolysaccharide (LPS), a component of Gram-negative bacteria, mediating monocyte activation.
- The precise triggers and implications of sCD14 release in various inflammatory contexts remain incompletely understood.
Purpose of the Study:
- To investigate the induction of soluble CD14 (sCD14) release by inflammatory cytokines.
- To determine if Toll-like receptor (TLR) ligands other than LPS influence CD14 expression on monocytes.
- To establish whether sCD14 serves as a general marker for monocyte activation.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were cultured from healthy donors.
- Cell cultures were stimulated with inflammatory cytokines.
- Monocyte surface CD14 expression and sCD14 levels in culture supernatants were measured following stimulation with various TLR ligands, including LPS.
Main Results:
- Inflammatory cytokines were demonstrated to induce the release of sCD14 from PBMCs.
- Toll-like receptor (TLR) ligands, distinct from LPS, were shown to decrease the expression of CD14 on the surface of monocytes.
- These results indicate that sCD14 release is not exclusively triggered by LPS.
Conclusions:
- Soluble CD14 (sCD14) is a marker of monocyte activation induced by inflammatory cytokines.
- The findings broaden the understanding of CD14 regulation, suggesting sCD14 reflects monocyte activation in response to diverse inflammatory stimuli, not solely LPS.
- This has implications for understanding inflammatory processes in infectious diseases like HIV.
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