In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 9 ( 2022-9-9), p. e0010774-
Abstract:
Currently, inflammatory bowel disease (IBD) has become a global chronic idiopathic disease with ever-rising morbidity and prevalence. Accumulating evidence supports the IBD-hygiene hypothesis that helminths and their derivatives have potential therapeutic value for IBD. Clonorchis sinensis ( C . sinensis ) mainly elicit Th2/Treg-dominated immune responses to maintain long-term parasitism in the host. This study aimed to evaluate the therapeutic effects of cysteine protease ( Cs CP) and adult crude antigen ( Cs CA) of C . sinensis , and C . sinensis ( Cs ) infection on DSS-induced colitis mice. Methods BALB/c mice were given 5% DSS daily for 7 days to induce colitis. During this period, mice were treated with r Cs CP, Cs CA or dexamethasone (DXM) every day, or Cs infection which was established in advance. Changes in body weight, disease activity index (DAI), colon lengths, macroscopic scores, histopathological findings, myeloperoxidase (MPO) activity levels, regulatory T cell (Treg) subset levels, colon gene expression levels, serum cytokine levels, and biochemical indexes were measured. Results Compared with Cs infection, r Cs CP and Cs CA alleviated the disease activity of acute colitis more significant without causing abnormal blood biochemical indexes. In comparison, r Cs CP was superior to Cs CA in attenuating colonic pathological symptoms, enhancing the proportion of Treg cells in spleens and mesenteric lymph nodes, and improving the secretion of inflammatory-related cytokines (e.g., IL-2, IL-4, IL-10 and IL-13) in serum. Combined with RNA-seq data, it was revealed that Cs CA might up-regulate the genes related to C-type lectin receptor and intestinal mucosal repair related signal pathways (e.g., Cd209d, F13a1 and Cckbr) to reduce colon inflammation and benefit intestinal mucosal repair. Dissimilarly, r Cs CP ameliorated colitis mainly through stimulating innate immunity, such as Toll like receptor (TLR) signaling pathway, down-regulating the expression of inflammatory cytokines (e.g., IL-12b, IL-23r and IL-7), thereby restraining the differentiation of Th1/Th17 cells. Conclusions Both r Cs CP and Cs CA showed good therapeutic effects on the treatment of acute colitis, but r Cs CP is a better choice. r Cs CP is a safe, effective, readily available and promising therapeutic agent against IBD mainly by activating innate immunity and regulating the IL-12/IL-23r axis.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010774
DOI:
10.1371/journal.pntd.0010774.g001
DOI:
10.1371/journal.pntd.0010774.g002
DOI:
10.1371/journal.pntd.0010774.g003
DOI:
10.1371/journal.pntd.0010774.g004
DOI:
10.1371/journal.pntd.0010774.g005
DOI:
10.1371/journal.pntd.0010774.g006
DOI:
10.1371/journal.pntd.0010774.g007
DOI:
10.1371/journal.pntd.0010774.g008
DOI:
10.1371/journal.pntd.0010774.t001
DOI:
10.1371/journal.pntd.0010774.s001
DOI:
10.1371/journal.pntd.0010774.s002
DOI:
10.1371/journal.pntd.0010774.s003
DOI:
10.1371/journal.pntd.0010774.s004
DOI:
10.1371/journal.pntd.0010774.s005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
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