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Updated: Jun 16, 2026
Establishment of an In vitro System to Study Intracellular Behavior of Candida glabrata in Human THP-1 Macrophages
Published on: December 10, 2013
Transdifferentiated BLaER1 cells as a genetically tractable model to study the interaction of pathogenic fungi with
Johannes Sonnberger1, Erik Böhm1, Janik Adriana Tomás-Morales1
1Department of Microbial Pathogenicity Mechanisms, Hans Knöll Institute, 07745 Jena, Germany.
Abstract:
Macrophages are essential in the defense against fungal disease. Elucidating antimicrobial mechanisms of macrophages and pathogen activities to evade these phagocytes will help in understanding fungal infections. Existing experimental models, however, have a number of disadvantages. Human macrophage-like cell lines offer genetic tractability, but often display reduced antifungal activity and altered phenotypes compared to primary cells. In contrast, primary human monocyte-derived macrophages closely reflect physiological responses but their use is constrained by donor variability, limited availability and restricted genetic manipulability. Here, we establish transdifferentiated BLaER1 cells as a human-derived, highly potent and genetically tractable infection model to study fungal-host interactions. We show that BLaER1 cells display macrophage characteristics and rapidly phagocytose cells of the major fungal pathogens Candida albicans, C. glabrata and C. auris. BLaER1 cells form functional phagolysosomes and elicit pro-inflammatory immune responses. Using knockout BLaER1 cells, we demonstrate for the first time in a human macrophage model that the host factor gasdermin D and the fungal peptide toxin candidalysin have distinct roles in triggering pyroptosis and inducing lytic host cell death.
Insights
Transdifferentiated BLaER1 cells offer a potent, genetically tractable human model for studying fungal infections. These cells mimic primary macrophages, revealing distinct roles for gasdermin D and candidalysin in host cell death during fungal encounters.
Area of Science:
- Immunology
- Microbiology
- Cell Biology
Background:
- Macrophages are crucial for combating fungal infections.
- Current experimental models have limitations: cell lines lack potency, and primary cells are difficult to manipulate.
- A need exists for a human-derived, genetically tractable model for fungal-host interaction studies.
Purpose of the Study:
- To establish and validate transdifferentiated BLaER1 cells as a robust human infection model for studying fungal-host interactions.
- To compare the antifungal capabilities of BLaER1 cells with existing models.
- To investigate the roles of specific host and fungal factors in triggering cell death during fungal infections.
Main Methods:
- Transdifferentiation of BLaER1 cells to a macrophage-like state.
- Assessment of phagocytosis and killing of Candida species (C. albicans, C. glabrata, C. auris).
- Analysis of phagolysosome formation, pro-inflammatory responses, and pyroptosis induction using knockout BLaER1 cells.
Main Results:
- BLaER1 cells exhibit macrophage characteristics, including potent phagocytosis of major fungal pathogens.
- These cells form functional phagolysosomes and mount pro-inflammatory responses.
- Distinct roles for gasdermin D and candidalysin in pyroptosis and lytic cell death were identified in this human macrophage model.
Conclusions:
- Transdifferentiated BLaER1 cells provide a valuable, genetically tractable human model for fungal infection research.
- This model advances understanding of macrophage antimicrobial mechanisms and fungal evasion strategies.
- The study elucidates key host-pathogen interactions leading to cell death during Candida infections.
