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Updated: Jun 7, 2025
In Vitro Phagocytosis of Myelin Debris by Bone Marrow-Derived Macrophages
Published on: December 30, 2017
Staphylococcus epidermidis alters macrophage polarization and phagocytic uptake by extracellular DNA release in vitro
Samira Weißelberg1, Anna Both1, Antonio Virgilio Failla2
1Institut für Medizinische Mikrobiologie, Virologie und Hygiene, Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany.
Abstract:
Biofilm formation shields Staphylococcus epidermidis from host defense mechanisms, contributing to chronic implant infections. Using wild-type S. epidermidis 1457, a PIA-negative mutant (1457-M10), and an eDNA-negative mutant (1457ΔatlE), this study examined the influence of biofilm matrix components on human monocyte-derived macrophage (hMDM) interactions. The wild-type strain was resistant to phagocytosis and induced an anti-inflammatory response in hMDMs, while both mutants were more susceptible to phagocytosis and triggered a pro-inflammatory response. Removing eDNA from the 1457 biofilm matrix increased hMDM uptake and a pro-inflammatory reaction, whereas adding eDNA to the 1457ΔatlE mutant reduced phagocytosis and promoted an anti-inflammatory response. Inhibiting TLR9 enhanced bacterial uptake and induced a pro-inflammatory response in hMDMs exposed to wild-type S. epidermidis. This study highlights the critical role of eDNA in immune evasion and the central role of TLR9 in modulating macrophage responses, advancing the understanding of implant infections.
Insights
Staphylococcus epidermidis biofilms use extracellular DNA (eDNA) to evade immune cells like macrophages. Blocking Toll-like receptor 9 (TLR9) enhances macrophage response to these biofilms, crucial for understanding implant infections.
Area of Science:
- Microbiology
- Immunology
- Biomedical Engineering
Background:
- Biofilm formation by *Staphylococcus epidermidis* is a major cause of chronic implant-associated infections.
- Biofilms protect bacteria from host immune defenses and antibiotic treatments.
- Key biofilm matrix components influencing host-pathogen interactions remain incompletely understood.
Purpose of the Study:
- To investigate the role of biofilm matrix components, specifically extracellular DNA (eDNA), in *S. epidermidis* interactions with human monocyte-derived macrophages (hMDMs).
- To elucidate the involvement of Toll-like receptor 9 (TLR9) in the host immune response to *S. epidermidis* biofilms.
Main Methods:
- Comparative analysis of wild-type *S. epidermidis* 1457, a PIA-negative mutant (1457-M10), and an eDNA-negative mutant (1457ΔatlE) in co-culture with hMDMs.
- Assessment of bacterial phagocytosis by hMDMs.
- Measurement of inflammatory cytokine production by hMDMs.
- Inhibition of TLR9 signaling pathway to evaluate its role in macrophage response.
Main Results:
- Wild-type *S. epidermidis* biofilms resisted phagocytosis and induced an anti-inflammatory response in hMDMs.
- Mutants lacking PIA or eDNA were more susceptible to phagocytosis and elicited a pro-inflammatory response.
- Removal of eDNA enhanced hMDM phagocytosis and pro-inflammatory cytokine release.
- Addition of eDNA to eDNA-deficient mutants reduced phagocytosis and promoted anti-inflammatory responses.
- Inhibition of TLR9 increased bacterial uptake and pro-inflammatory cytokine production in hMDMs exposed to wild-type *S. epidermidis*.
Conclusions:
- Extracellular DNA (eDNA) is a critical component of *S. epidermidis* biofilms that facilitates immune evasion by modulating macrophage responses.
- Toll-like receptor 9 (TLR9) plays a central role in recognizing *S. epidermidis* biofilms and orchestrating the subsequent macrophage inflammatory response.
- Targeting eDNA or TLR9 signaling presents potential therapeutic strategies for managing *S. epidermidis*-associated implant infections.
