Clostridium Perfringens Alpha Toxin Inhibits Granulocyte Colony-Stimulating Factor

Juezhou Shen
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Abstract

Clostridium perfringens is a gram-positive spore-forming anaerobic bacteria. C. perfringens is one of the most common causes of food poisoning illness and has a high mortality rate. As a growth factor, granulocyte colony-stimulating factor helps immune system maintain the balanced numbers of neutrophils when we are infected by pathogens. Clostridium perfringens alpha toxin promotes the formation of G-CSF. During the bacterial infection, lipopolysaccharide (LPS) is sensed through a Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88)-dependent pathway. This leads to the increased secretion of G-CSF into the systemic circulation which accelerated the proliferation and differentiation of neutrophils. However, Clostridium perfringens impairs the granulopoiesis by decreasing the surface expression of neutrophil Ly6G+. The study will use mice, which were separate into positive control groups with C. perfringens injection and negative control group with phosphate-buffered saline. Employing a variety of procedures and methods, in vivo, such as FACS and ELISA, the paper investigates whether C. perfringens alpha toxin would inhibit granulocyte colony-stimulating factor, impairing granulopoiesis and inhibiting G-CSF-mediated cell proliferation of Ly6G+ neutrophils in a productive and effective way.
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产气荚膜梭菌α毒素抑制粒细胞集落刺激因子
产气荚膜梭菌是革兰氏阳性芽孢形成厌氧菌。产气荚膜梭菌是引起食物中毒的最常见原因之一,死亡率很高。粒细胞集落刺激因子作为一种生长因子,在人体受到病原体感染时,帮助免疫系统维持中性粒细胞数量的平衡。产气荚膜梭菌α毒素促进G-CSF的形成。在细菌感染过程中,脂多糖(LPS)通过toll样受体4 (TLR4)和髓样分化因子88 (MyD88)依赖途径被感知。这导致G-CSF分泌增加进入体循环,加速了中性粒细胞的增殖和分化。然而,产气荚膜梭菌通过降低中性粒细胞Ly6G+的表面表达而损害颗粒生成。该研究将使用小鼠,将其分为注射产气荚膜原梭菌的阳性对照组和注射磷酸盐缓冲盐水的阴性对照组。采用多种程序和方法,在体内,如FACS和ELISA,研究产气荚膜荚膜球菌α毒素是否能有效抑制粒细胞集落刺激因子,损害粒细胞生成,抑制g - csf介导的Ly6G+中性粒细胞的细胞增殖。
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