Cadmium ingestion exacerbates Salmonella infection, with a loss of goblet cells through activation of Notch signaling pathways by ROS in the intestine

JOURNAL OF HAZARDOUS MATERIALS

卷:391

Article

Xie, Shuang¹  Jiang, Lan¹  Wang, Minjuan¹  Sun, Wenjing¹  Yu, Siyong¹  Turner, Jerrold R.^2,3  Yu, Qinghua¹ 

[1] Nanjing Agr Univ, Coll Vet Med, MOE Joint Int Res Lab Anim Hlth & Food Safety, Weigang 1, Nanjing 210095, Jiangsu, Peoples R China

[2] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Dept Med, Div Gastroenterol Hepatol & Endoscopy, 75 Francis St, Boston, MA 02115 USA

关键词: Cadmium;    Intestinal barrier;    Enteropathogens;    Goblet cells;    Notch signaling pathway;   

DOI  :  10.1016/j.jhazmat.2020.122262

来源: Elsevier

【 摘 要 】

Whether cadmium ingestion affects the susceptibility to infection and the detailed mechanism have not been investigated. We aimed to evaluate the effects of cadmium on the intestinal mucosal barrier and Salmonella infection. We found that oral administration of cadmium caused damage to the intestinal mucosal barrier, with body weight loss, an increase in inflammation, significantly reduced Muc2 expression and goblet cell loss in the intestine. The effect of cadmium on secretory cell differentiation was further demonstrated to be regulated by the overactivation of the Notch signaling pathway by increased production of ROS both in mice and in intestinal organoids. The damage of cadmium to the intestinal barrier, and goblet cell and Paneth cells loss, dramatically increased susceptibility to enteropathogensinfection at a low dose (10(2) CFU), with a high death ratio, body weight loss and severe intestinal inflammation. However, enteropathogens susceptibility and intestinal barrier damage enhanced by cadmium was alleviated by inhibiting ROS production and Notch pathway activation, with reversion of goblet cell loss. This study indicated cadmium didn't only affect the integrity of intestinal barrier and epithelial differentiation, but also increased the risk of enteropathogenic infection from food contamination or environmental pollution, which signals an alarm for public health.

【 授权许可】

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