Abstract
Clostridium perfringens α-toxin induces hemolysis of erythrocytes from various species, but it has not been elucidated whether the toxin affects erythropoiesis. In this study, we treated bone marrow cells (BMCs) from mice with purified α-toxin and found that TER119+ erythroblasts were greatly decreased by the treatment. A variant α-toxin defective in enzymatic activities, phospholipase C and sphingomyelinase, had no effect on the population of erythroblasts, demonstrating that the decrease in erythroblasts was dependent of its enzymatic activities. α-Toxin reduced the CD71+TER119+ and CD71–TER119+ cell populations but not the CD71+TER119− cell population. In addition, α-toxin decreased the number of colony-forming unit erythroid colonies but not burst-forming unit erythroid colonies, indicating that α-toxin preferentially reduced mature erythroid cells compared with immature cells. α-Toxin slightly increased annexinV+ cells in TER119+ cells. Additionally, simultaneous treatment of BMCs with α-toxin and erythropoietin greatly attenuated the reduction of TER119+ erythroblasts by α-toxin. Furthermore, hemin-induced differentiation of human K562 erythroleukemia cells was impaired by α-toxin, whereas the treatment exhibited no apparent cytotoxicity. These results suggested that α-toxin mainly inhibited erythroid differentiation. Together, our results provide new insights into the biological activities of α-toxin, which might be important to understand the pathogenesis of C. perfringens infection.
Highlights
Clostridium perfringens α-toxin, which is a major virulence factor during C. perfringens infection, is known to have two enzyme activities, phospholipase C (PLC) and sphingomyelinase (SMase), and these activities has been shown to be involved in various biological activities[1, 2]
Α-toxin affects a broad range of cell lines and induces various biological activities that are important to understand the pathogenesis of C. perfringens infection
We treated the cells with α-toxin for 3, 6, or 24 h, and found that the decrease in TER119+ cells had already been induced after 3 h of treatment, and TER119+ cells decreased gradually up to 24 h, which meant that the reduction in TER119+ erythroblasts by α-toxin was time dependent (Fig. 1C,D)
Summary
Clostridium perfringens α-toxin, which is a major virulence factor during C. perfringens infection, is known to have two enzyme activities, phospholipase C (PLC) and sphingomyelinase (SMase), and these activities has been shown to be involved in various biological activities[1, 2]. Α-toxin has been reported to directly disrupt cell membrane and cause cytolysis[9,10,11]. These biological activities are proposed to play major roles in C. perfringens-induced myonecrosis. Α-toxin affects a broad range of cell lines and induces various biological activities that are important to understand the pathogenesis of C. perfringens infection. Bacillus anthracis lethal toxin, which induces hemolysis in vitro, was reported to suppress erythropoiesis by killing erythroid progenitors and inhibit erythroid differentiation of cord blood-derived CD34+ hematopoietic stem cells[19]. We demonstrate that C. perfringens α-toxin impairs erythroid differentiation, providing a new insight into the biological activities of α-toxin
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