Dataset Information

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

ABSTRACT:

Background

Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear.

Methods

Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treated with T.s. In vitro experiments, the LPS combination with ATP was used to induce the pyroptosis model, followed by intervention with crude protein from T.s (T.s cp). Additionally, the pyroptosis agonist of NSC or the pyroptosis inhibitor vx-765 was added to intervene to explore the role of pyroptosis in DSS-induced acute colitis. The degree of pyroptosis was evaluated by western blot, qPCR and IHC, etc., in vivo and in vitro.

Results

T.s intervention significantly inhibited NLRP3 inflammasome activation and GSDMD-mediated pyroptosis by downregulating the expression of pyroptosis-related signatures in vitro (cellular inflammatory model) and in vivo (DSS-induced UC mice model). Furthermore, blockade of GSDMD-mediated pyroptosis by the caspase-1 inhibitor vx-765 has a similar therapeutic effect on DSS-induced UC mice with T.s intervention, thus indicating that T.s intervention alleviated DSS-induced UC in mice by inhibiting GSDMD-mediated pyroptosis.

Conclusion

This study showed that T.s could alleviate the pathological severity UC via GSDMD-mediated pyroptosis, and it provides new insight into the mechanistic study and application of helminths in treating colitis.

SUBMITTER: Ma ZR

PROVIDER: S-EPMC10424392 | biostudies-literature | 2023 Aug

REPOSITORIES: biostudies-literature

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Publications

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

Ma Zhen-Rong ZR Li Zhuo-Lin ZL Zhang Ni N Lu Bin B Li Xuan-Wu XW Huang Ye-Hong YH Nouhoum Dibo D Liu Xian-Shu XS Xiao Ke-Chun KC Cai Li-Ting LT Xu Shao-Rui SR Yang Xue-Xian O XO Huang Shuai-Qin SQ Wu Xiang X

Parasites & vectors 20230814 1

<h4>Background</h4>Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is increasing worldwide. Although there is currently no completely curative treatment, helminthic therapy shows certain therapeutic potential for UC. Many studies have found that Trichinella spiralis (T.s) has a protective effect on UC, but the specific mechanism is still unclear.<h4>Methods</h4>Balb/c mice drank dextran sulfate sodium (DSS) to induce acute colitis and then were treat ...[more]

PMID: 37580819

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Project description:Publication of the genome from the clade I organism, Trichinella spiralis, has provided us an avenue to address more holistic problems in parasitology; namely the processes of adaptation and the evolution of parasitism. Parasitism among nematodes has evolved in multiple, independent events. Deciphering processes that drive species diversity and adaptation are keys to understanding parasitism and advancing control strategies. Studies have been put forth on morphological and physiological aspects of parasitism and adaptation in nematodes; however, data is now coming available to investigate adaptation, host switching and parasitism at the genomic level. Herein we compare proteomic data from the clade I parasite, Trichinella spiralis with data from Brugia malayi (clade III), Meloidogyne hapla and Meloidogyne incognita (clade IV), and free-living nematodes belonging to the genera Caenorhabditis and Pristionchus (clade V). We explore changes in protein family birth/death and expansion/reduction over the course of metazoan evolution using Homo sapiens, Drosophila melanogaster and Saccharomyces cerevisiae as outgroups for the phylum Nematoda. We further examine relationships between these changes and the ability and/or result of nematodes adapting to their environments. Data are consistent with gene loss occurring in conjunction with nematode specialization resulting from parasitic worms acclimating to well-defined, environmental niches. We observed evidence for independent, lateral gene transfer events involving conserved genes that may have played a role in the evolution of nematode parasitism. In general, parasitic nematodes gained proteins through duplication and lateral gene transfer, and lost proteins through random mutation and deletions. Data suggest independent acquisition rather than ancestral inheritance among the Nematoda followed by selective gene loss over evolutionary time. Data also show that parasitism and adaptation affected a broad range of proteins, especially those involved in sensory perception, metabolism, and transcription/translation. New protein gains with functions related to regulating transcription and translation, and protein family expansions with functions related to morphology and body development have occurred in association with parasitism. Further gains occurred as a result of lateral gene transfer and in particular, with the cyanase protein family In contrast, reductions and/or losses have occurred in protein families with functions related to metabolic process and signal transduction. Taking advantage of the independent occurrences of parasitism in nematodes, which enabled us to distinguish changes associated with parasitism from species specific niche adaptation, our study provides valuable insights into nematode parasitism at a proteome level using T. spiralis as a benchmark for early adaptation to or acquisition of parasitism.

Project description:BackgroundTrichinellosis is a meat-borne zoonotic disease caused by parasites of the genus Trichinella. To date, 12 taxa have been described. The identification of Trichinella species is crucial in order to identify the possible source of infection, the geographical origin of the parasite and to assess risk of infection for domestic pigs and humans. Specific identification of the etiological agent is not always feasible using direct methods since the source of infection can be untraceable. The aim of this study was to develop a diagnostic tool to infer the causative Trichinella species using western blot patterns of sera derived from infected animal and human hosts.MethodsSera from mice experimentally infected with Trichinella spiralis, Trichinella britovi, Trichinella pseudospiralis and Trichinella papuae were tested by western blot using homologous and heterologous crude worm extracts (CWE) and a highly sensitive detection system based on chemiluminescence. In addition, sera from pigs experimentally infected with T. spiralis, T. britovi and T. pseudospiralis and from patients with confirmed T. spiralis, T. britovi and T. pseudospiralis infections, were also included.ResultsSera from mice infected with one Trichinella species reacted with CWE proteins from all four investigated species. Likewise, sera derived from pigs and humans infected with one Trichinella species reacted with CWE proteins from all the three investigated species. Using T. spiralis CWE, sera from T. pseudospiralis-infected hosts yielded a characteristic pattern of reactivity using Wb, which differed to that produced by T. spiralis/T. britovi- or T. papuae-infected host sera.ConclusionsThe present study suggests that western blot using T. spiralis CWE may be a useful tool to distinguish Trichinella infections caused by T. pseudospiralis from those caused by T. spiralis or T. britovi. This method may support epidemiological investigations, particularly when the source of infection is not traceable.

Dataset Information

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

Background

Methods

Results

Conclusion

Publications

Inhibition of GSDMD-mediated pyroptosis triggered by Trichinella spiralis intervention contributes to the alleviation of DSS-induced ulcerative colitis in mice.

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