Bacterial pore-forming toxin pneumolysin: Cell membrane structure and microvesicle shedding capacity determines differential survival of immune cell types

Larpin, Yu; Besançon, Hervé; Iacovache, Mircea Ioan; Babiychuk, Victoriia S.; Babiychuk, Eduard B.; Zuber, Benoît; Draeger, Annette; Köffel, René (2020). Bacterial pore-forming toxin pneumolysin: Cell membrane structure and microvesicle shedding capacity determines differential survival of immune cell types. FASEB journal, 34(1), pp. 1665-1678. Federation of American Societies for Experimental Biology 10.1096/fj.201901737RR

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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.

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