Related Experiment Videos
Peptidoglycan and lipoteichoic acid modify monocyte phenotype in human whole blood
P F Jørgensen1, J E Wang, M Almlöf
1Institute for Surgical Research, University of Oslo, The National Hospital, N-0027 Oslo, Norway. p.f.jorgensen@klinmed.uio.no
Abstract:
We examined the influence of the gram-positive cell wall products peptidoglycan (PepG) and lipoteichoic acid (LTA), compared to lipopolysaccharide (LPS), on the monocyte expression of receptors involved in antigen presentation (HLA-DR, B7.1, and B7.2), cell adhesion (intercellular adhesion molecule-1 [ICAM-1] and lymphocyte function associated antigen-3 [LFA-3]), phagocytosis (Fc gamma RI), and cell activation (CD14). We also evaluated possible influences of the immunosuppressive drugs cyclosporine A, tacrolimus, and sirolimus on the expression of these receptors. Pretreatment of whole blood for 4 h with the immunosuppressive drugs did not influence the expression of the surface receptors in normal or stimulated blood. Stimulation with both PepG and LTA caused significant up-regulation of the surface expression of ICAM-1 and HLA-DR on whole blood monocytes, similar to that obtained with LPS, whereas B7.1, B7.2, LFA-3, and Fc gamma RI were not modulated. PepG and LTA also caused increased expression of CD14, whereas LPS down-regulated this molecule. In contrast, we did not detect any significant influence of any of the bacterial products on the plasma concentration of soluble CD14. We hypothesized that the increased expression of surface CD14 in blood stimulated with PepG would prime for cellular activation by LPS. Indeed, we show that PepG and the partial PepG structure muramyl dipeptide acted in synergy with LPS to cause the release of tumor necrosis factor-alpha. The results suggest that PepG and LPS provoke partly different responses on monocyte phenotype and that CD14 may play different roles in the innate response to gram-positive and gram-negative bacteria.
Insights
Gram-positive bacterial products peptidoglycan (PepG) and lipoteichoic acid (LTA) up-regulate monocyte ICAM-1 and HLA-DR, unlike LPS. PepG and LTA also increase CD14 expression, priming monocytes for activation by LPS.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Monocytes play a crucial role in innate and adaptive immunity.
- Bacterial cell wall components differentially modulate monocyte responses.
- Understanding these interactions is key to developing immunotherapies.
Purpose of the Study:
- To investigate the effects of gram-positive peptidoglycan (PepG) and lipoteichoic acid (LTA) on monocyte receptor expression.
- To compare these effects with those of gram-negative lipopolysaccharide (LPS).
- To assess the impact of immunosuppressive drugs on these responses.
Main Methods:
- Whole blood assays were used to measure monocyte surface receptor expression.
- Stimulation with PepG, LTA, and LPS was performed.
- Expression of receptors for antigen presentation, adhesion, phagocytosis, and cell activation was analyzed.
- Effects of cyclosporine A, tacrolimus, and sirolimus were evaluated.
Main Results:
- PepG and LTA significantly upregulated intercellular adhesion molecule-1 (ICAM-1) and HLA-DR on monocytes.
- Unlike LPS, PepG and LTA increased CD14 expression.
- Immunosuppressive drugs did not affect receptor expression.
- PepG and muramyl dipeptide synergized with LPS to induce TNF-alpha release.
Conclusions:
- PepG and LPS induce distinct monocyte phenotype changes.
- CD14 may have differential roles in responding to gram-positive versus gram-negative bacteria.
- PepG primes monocytes for enhanced activation by LPS, highlighting synergistic innate immune responses.