Streptolysin O hijacks the membrane repair system to blind natural killer cell (INM3P.405)

Abstract

Abstract The pore-forming toxin Streptolysin O (SLO) secreted by Group A Streptococcus binds to cholesterol and oligomerizes on the membrane to form a lytic pore. Immune cells survive pore-formation through a Ca2+ dependent process that sequesters and sheds pores on vesicles. These vesicles are enriched in cholesterol and glycosylphosphatidylinositol (GPI)-anchored proteins, raising the possibility that immune receptors are shed during the repair process. NKG2D, IL-18 receptor and IL-12 receptor promote Interferon-γ (IFNγ) production in natural killer (NK) cells and all associate with cholesterol-rich microdomains or GPI-anchored proteins. Here we found SLO challenge impaired IFNγ secretion from NK cells when stimulated with K562 cells or IL-12 and IL-18 without affecting NK cell viability. We found that the IL-12 Receptor β1 was shed from NK cells on microvesicles along with SLO in a Ca2+ dependent fashion. These data suggest that shedding of activation receptors during membrane repair impairs NK cell function. Taken together, these data describe one way in which bacterial toxins can hijack membrane repair to blind cells to the presence of pathogens.