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Updated: Dec 31, 2025
High-throughput Measurement of Plasma Membrane Resealing Efficiency in Mammalian Cells
Published on: January 7, 2019
Bacterial pore-forming toxin pneumolysin: Cell membrane structure and microvesicle shedding capacity determines
Yu Larpin1, Hervé Besançon1, Mircea-Ioan Iacovache2
1Department of Cell Biology, Institute of Anatomy, University of Bern, Bern, Switzerland.
Abstract:
Bacterial infectious diseases can lead to death or to serious illnesses. These outcomes are partly the consequence of pore-forming toxins, which are secreted by the pathogenic bacteria (eg, pneumolysin of Streptococcus pneumoniae). Pneumolysin binds to cholesterol within the plasma membrane of host cells and assembles to form trans-membrane pores, which can lead to Ca2+ influx and cell death. Membrane repair mechanisms exist that limit the extent of damage. Immune cells which are essential to fight bacterial infections critically rely on survival mechanisms after detrimental pneumolysin attacks. This study investigated the susceptibility of different immune cell types to pneumolysin. As a model system, we used the lymphoid T-cell line Jurkat, and myeloid cell lines U937 and THP-1. We show that Jurkat T cells are highly susceptible to pneumolysin attack. In contrast, myeloid THP-1 and U937 cells are less susceptible to pneumolysin. In line with these findings, human primary T cells are shown to be more susceptible to pneumolysin attack than monocytes. Differences in susceptibility to pneumolysin are due to (I) preferential binding of pneumolysin to Jurkat T cells and (II) cell type specific plasma membrane repair capacity. Myeloid cell survival is mostly dependent on Ca2+ induced expelling of damaged plasma membrane areas as microvesicles. Thus, in myeloid cells, first-line defense cells in bacterial infections, a potent cellular repair machinery ensures cell survival after pneumolysin attack. In lymphoid cells, which are important at later stages of infections, less efficient repair mechanisms and enhanced toxin binding renders the cells more sensitive to pneumolysin.
Insights
Pore-forming toxins like pneumolysin harm immune cells. This study shows T cells are highly susceptible, while myeloid cells survive better due to superior membrane repair mechanisms.
Area of Science:
- Immunology
- Cell Biology
- Microbiology
Background:
- Pore-forming toxins, such as pneumolysin from Streptococcus pneumoniae, cause severe illness and death by damaging host cells.
- These toxins create pores in cell membranes, leading to calcium influx and cell death, necessitating cellular defense and repair mechanisms.
Purpose of the Study:
- To investigate the differential susceptibility of various immune cell types to pneumolysin.
- To elucidate the underlying mechanisms, including toxin binding and membrane repair capacity, that contribute to cell type-specific responses to pneumolysin.
Main Methods:
- Utilized lymphoid (Jurkat) and myeloid (U937, THP-1) cell lines as model systems.
- Compared the susceptibility of these cell lines and primary human T cells and monocytes to pneumolysin.
- Analyzed differences in pneumolysin binding and cellular membrane repair mechanisms.
Main Results:
- Jurkat T cells and primary T cells exhibited high susceptibility to pneumolysin.
- Myeloid cell lines (U937, THP-1) and primary monocytes demonstrated lower susceptibility.
- Differences were attributed to preferential pneumolysin binding in T cells and superior calcium-mediated microvesicle expulsion for membrane repair in myeloid cells.
Conclusions:
- Immune cell susceptibility to pneumolysin varies significantly based on cell type.
- Myeloid cells possess robust membrane repair mechanisms, ensuring survival against pneumolysin, crucial for their role as first-line defenders.
- T cells, important in later infection stages, are more vulnerable due to less efficient repair and greater toxin binding.
