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Updated: Aug 13, 2025
Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Gram-Positive Bacteria Cell Wall Peptidoglycan Polymers Activate Human Dendritic Cells to Produce IL-23 and IL-1β and
Sean Turner1, Brent Raisley1, Kimberly Roach1
1Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK 73104, USA.
Abstract:
Gram-positive bacterial infections are a major cause of organ failure and mortality in sepsis. Cell wall peptidoglycan (PGN) is shed during bacterial replication, and Bacillus anthracis PGN promotes a sepsis-like pathology in baboons. Herein, we determined the ability of polymeric Bacillus anthracis PGN free from TLR ligands to shape human dendritic cell (DC) responses that are important for the initiation of T cell immunity. Monocyte-derived DCs from healthy donors were incubated with PGN polymers isolated from Bacillus anthracis and Staphylococcus aureus. PGN activated the human DCs, as judged by the increased expression of surface HLA-DR, CD83, the T cell costimulatory molecules CD40 and CD86, and the chemokine receptor CCR7. PGN elicited the DC production of IL-23, IL-6, and IL-1β but not IL-12p70. The PGN-stimulated DCs induced the differentiation of naïve allogeneic CD4+ T cells into T helper (TH) cells producing IL-17 and IL-21. Notably, the DCs from a subset of donors did not produce significant levels of IL-23 and IL-1β upon PGN stimulation, suggesting that common polymorphisms in immune response genes regulate the PGN response. In sum, purified PGN is a highly stimulatory cell wall component that activates human DCs to secrete proinflammatory cytokines and promote the differentiation of TH17 cells that are important for neutrophil recruitment in extracellular bacterial infections.
Insights
Bacterial peptidoglycan (PGN) activates human dendritic cells (DCs), promoting T helper 17 (TH17) cell differentiation crucial for fighting infections. Donor variations in immune responses to PGN were observed.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Gram-positive bacterial infections, particularly sepsis, lead to significant organ failure and mortality.
- Bacterial cell wall peptidoglycan (PGN) is implicated in sepsis pathology, as demonstrated by Bacillus anthracis PGN in baboons.
- Understanding how PGN influences the human immune system is critical for developing effective treatments.
Purpose of the Study:
- To investigate the capacity of purified Bacillus anthracis PGN, devoid of TLR ligands, to modulate human dendritic cell (DC) responses.
- To determine the impact of PGN on DC activation, cytokine production, and subsequent T cell differentiation.
- To explore potential variations in DC responses to PGN among different donors.
Main Methods:
- Monocyte-derived DCs from healthy donors were incubated with purified PGN polymers from Bacillus anthracis and Staphylococcus aureus.
- DC activation was assessed by measuring surface marker expression (HLA-DR, CD83, CD40, CD86, CCR7).
- Cytokine production (IL-23, IL-6, IL-1β, IL-12p70) by DCs and T helper (TH) cell differentiation (IL-17, IL-21) were analyzed.
Main Results:
- PGN significantly activated human DCs, indicated by increased expression of key surface molecules.
- PGN stimulated DCs to produce IL-23, IL-6, and IL-1β, but not IL-12p70.
- PGN-stimulated DCs promoted the differentiation of naive CD4+ T cells into IL-17 and IL-21 producing TH17 cells.
- A subset of donors exhibited reduced IL-23 and IL-1β production in response to PGN, suggesting genetic regulation.
Conclusions:
- Purified bacterial PGN is a potent activator of human DCs, driving pro-inflammatory cytokine secretion.
- PGN-induced DC activation promotes TH17 cell differentiation, essential for combating extracellular bacterial infections and recruiting neutrophils.
- Inter-individual variability in DC responses to PGN highlights the role of host genetic factors.
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