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

• Published in: Journal of hazardous materials Vol. 391; p. 122262
• Main Authors: Xie, Shuang, Jiang, Lan, Wang, Minjuan, Sun, Wenjing, Yu, Siyong, Turner, Jerrold R., Yu, Qinghua
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 05.06.2020
• Subjects: Animals; Cadmium; Cadmium - pharmacokinetics; Cadmium - toxicity; Disease Progression; Enteropathogens; Goblet cells; Intestinal barrier; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Intestinal Mucosa - pathology; Jejunum - drug effects; Jejunum - metabolism; Jejunum - pathology; Lipopolysaccharides - blood; Liver - metabolism; Mice, Inbred C57BL; Notch signaling pathway; Reactive Oxygen Species - metabolism; Receptors, Notch - metabolism; Salmonella Infections - metabolism; Salmonella Infections - pathology; Signal Transduction; Tumor Necrosis Factor-alpha - metabolism; Cadmium; Intestinal barrier; Notch signaling pathway; Enteropathogens; Goblet cells
• ISSN: 0304-3894; 1873-3336
• DOI: 10.1016/j.jhazmat.2020.122262

[Display omitted] •Cadmium stimulated the production of ROS and then activated Notch pathway.•Cadmium exposure induced the loss of goblet cell and Paneth cells.•Cadmium exposure increased susceptibility to pathogens infection even at a low dose. 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 (102 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.