Human cathelicidin LL-37 exerts amelioration effects against EHEC O157:H7 infection regarding inflammation, enteric dysbacteriosis, and impairment of gut barrier function

• Published in: Peptides (New York, N.Y. : 1980) Vol. 159; p. 170903
• Main Authors: Fang, Xin, Nong, Keyi, Wang, Zihan, Jin, Yuanli, Gao, Feng, Zeng, Qiuyu, Wang, Xuemei, Zhang, Haiwen
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2023
• Subjects: Animals; Cathelicidins - pharmacology; Cathelicidins - therapeutic use; Cytokines; Disease Models, Animal; Dysbiosis - drug therapy; EHEC O157:H7; Escherichia coli Infections - drug therapy; Escherichia coli Infections - prevention & control; Escherichia coli O157 - physiology; Humans; Inflammation; Inflammation - drug therapy; Intestinal barrier; Intestinal microbiota; LL-37; PBS; PCoA; EHEC; Intestinal barrier; LL-37; IHC; E.coli; LDA; Inflammation; LEfSe; TUNEL; TJ; Intestinal microbiota; A/E; SEM; EHEC O157:H7; Stxs; EMB; CFUs; ELISA
• ISSN: 0196-9781; 1873-5169
• DOI: 10.1016/j.peptides.2022.170903

Enterohaemorrhagic Escherichia coli (EHEC) O157:H7 infection impairs intestinal barrier function, causing intestinal inflammation and enteric dysbacteriosis. The human cathelicidin LL-37 can regulate excessive inflammatory responses, barrier function, and balance the intestinal microbial community; however, little is known about its effects on inflammation, intestinal barrier function, and microbiota disorders in EHEC O157:H7-infected mice. In this study, we investigated the protective effect of LL-37 against EHEC O157:H7 infection and elucidated the underlying mechanism using a mouse model. LL-37 treatment was found to inhibit body weight loss, restore edema and destruction of the intestinal villi, and significantly reduce epithelial apoptosis (P < 0.05) in EHEC O157:H7-infected mice. Furthermore, inflammatory infiltration of macrophages and neutrophils into the jejunum and colon was significantly decreased (P < 0.05). LL-37 significantly downregulated the production of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) (P < 0.05) and upregulated the anti-inflammatory cytokine (IL-10) during EHEC O157:H7 infection. LL-37 increased the expression of tight junction proteins (ZO-1, ZO-2, claudin-1, and occludin), which are associated with intestinal barrier function, and had a positive effect on EHEC O157:H7-induced microbial disorders, particularly in terms of the inflammation-related microbiota. LL-37 also significantly decreased the E. coli load in the liver and spleen (P < 0.01) and restored the structure of the liver and kidney. Taken together, LL-37 conferred protection in a EHEC O157:H7-induced mouse model by reducing intestinal inflammation, enhancing intestinal barrier function, and restoring the balance of the intestinal microbiota, which indicates the therapeutic potential of LL-37 against pathogen infection. [Display omitted] •LL-37 alleviated the intestinal inflammation in EHEC O157:H7-induced mice.•LL-37 enhanced the intestinal barrier function by the up-regulation of tight junction proteins in EHEC O157:H7-induced mice.•LL-37 regulated the enteric dysbacteriosis EHEC O157:H7 caused.•LL-37 presented the protective effect against the infection of EHEC O157:H7.