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Updated: Sep 7, 2025
Reprograming Model of Human Monocyte-derived Macrophages for In-vitro Assays
Published on: April 18, 2025
Human macrophage polarization determines bacterial persistence of Staphylococcus aureus in a liver-on-chip-based
Fatina Siwczak1, Zoltan Cseresnyes2, Mohamed I Abdelwahab Hassan1
1Institute of Biochemistry II, Center for Sepsis Control and Care, Jena University Hospital, Am Nonnenplan 1, 07743, Jena, Germany.
Abstract:
Infections with Staphylococcus aureus (S. aureus) have been reported from various organs ranging from asymptomatic colonization to severe infections and sepsis. Although considered an extracellular pathogen, S. aureus can invade and persist in professional phagocytes such as monocytes and macrophages. Its capability to persist and manipulate macrophages is considered a critical step to evade host antimicrobial reactions. We leveraged a recently established human liver-on-chip model to demonstrate that S. aureus specifically targets macrophages as essential niche facilitating bacterial persistence and phenotype switching to small colony variants (SCVs). In vitro, M2 polarization was found to favor SCV-formation and was associated with increased intracellular bacterial loads in macrophages, increased cell death, and impaired recruitment of circulating monocytes to sites of infection. These findings expand the knowledge about macrophage activation in the liver and its impact on bacterial persistence and dissemination in the course of infection.
Insights
Staphylococcus aureus (S. aureus) invades liver macrophages, creating a niche for persistence and switching to small colony variants (SCVs). This macrophage activation impairs host defenses and promotes bacterial spread.
Area of Science:
- Microbiology
- Immunology
- Pathogen-host interactions
Background:
- Staphylococcus aureus (S. aureus) causes diverse infections, from colonization to sepsis.
- Despite being extracellular, S. aureus invades phagocytes like macrophages, crucial for immune evasion.
- Understanding S. aureus-macrophage interactions is key to controlling infections.
Purpose of the Study:
- To investigate S. aureus persistence and behavior within macrophages using a human liver-on-chip model.
- To determine the role of macrophage polarization in S. aureus infection dynamics.
Main Methods:
- Utilized a human liver-on-chip model for studying S. aureus infection.
- Analyzed macrophage polarization (M2) and its effect on S. aureus.
- Quantified intracellular bacterial loads, cell death, and monocyte recruitment.
Main Results:
- S. aureus specifically targets liver macrophages, establishing a persistent niche.
- M2-polarized macrophages promoted S. aureus small colony variant (SCV) formation.
- Increased intracellular bacterial load, macrophage cell death, and reduced monocyte recruitment were observed.
Conclusions:
- Liver macrophages serve as a critical niche for S. aureus persistence and SCV development.
- M2 macrophage polarization exacerbates S. aureus infection by promoting persistence and immune evasion.
- Findings offer insights into S. aureus pathogenesis and potential therapeutic targets in liver infections.
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