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预防性猪鞭虫卵(TSO)治疗可保护免疫功能正常的兔子免受 DSS 结肠炎的侵害,但在免疫抑制的情况下可能有害。

Preventive Trichuris suis ova (TSO) treatment protects immunocompetent rabbits from DSS colitis but may be detrimental under conditions of immunosuppression.

机构信息

Division of Gastroenterology and Hepatology USZ, Zurich, Switzerland.

Gastroenterology and Hepatology Division, Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, New York, USA.

出版信息

Sci Rep. 2017 Nov 28;7(1):16500. doi: 10.1038/s41598-017-16287-4.

DOI:10.1038/s41598-017-16287-4
PMID:29184071
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5705695/
Abstract

Trichuris suis ova (TSO) have been tested for therapeutic application in inflammatory bowel diseases (IBD) yet understanding of the underlying mechanisms and safety in an immunocompromised host is limited due to lack of a suitable animal model. We used a recently established rabbit model of dextran sodium sulphate (DSS) induced colitis to study the efficacy, mechanisms and safety of TSO therapy in immunocompetent and immunosuppressed animals. TSO treatment prevented the DSS induced weight loss, delayed the onset of DSS induced symptoms by 2 days and significantly reduced the disease activity (DAI). TSO treatment protected caecal histology and prevented the colitis-associated loss in faecal microbiota diversity. Mainly the transcriptome of lamina propria mononuclear cells (LPMC) was affected by TSO treatment, showing dampened innate and adaptive inflammatory responses. The protective effect of TSO was lost in immunosuppressed rabbits, where TSO exacerbated colitis. Our data show that preventive TSO treatment ameliorates colitis severity in immunocompetent rabbits, modulates LPMC immune responses and reduces faecal dysbiosis. In contrast, the same TSO treatment exacerbates colitis in immunosuppressed animals. Our data provide further evidence for a therapeutic effect of TSO in IBD, yet caution is required with regard to TSO treatment in immunosuppressed patients.

摘要

猪鞭虫卵(TSO)已被测试用于治疗炎症性肠病(IBD),但由于缺乏合适的动物模型,对于免疫功能低下宿主的潜在机制和安全性了解有限。我们使用最近建立的兔葡聚糖硫酸钠(DSS)诱导结肠炎模型来研究 TSO 治疗在免疫功能正常和免疫抑制动物中的疗效、机制和安全性。TSO 治疗可预防 DSS 诱导的体重减轻,使 DSS 诱导症状的发作延迟 2 天,并显著降低疾病活动度(DAI)。TSO 治疗可保护盲肠组织学并防止结肠炎相关的粪便微生物多样性丧失。主要是黏膜固有层单核细胞(LPMC)的转录组受到 TSO 治疗的影响,表现为先天和适应性炎症反应减弱。在免疫抑制的兔子中,TSO 的保护作用丧失,其中 TSO 加剧了结肠炎。我们的数据表明,预防性 TSO 治疗可改善免疫功能正常的兔子的结肠炎严重程度,调节 LPMC 的免疫反应并减少粪便失调。相比之下,相同的 TSO 治疗在免疫抑制的动物中加重了结肠炎。我们的数据为 TSO 在 IBD 中的治疗效果提供了进一步的证据,但需要谨慎对待免疫抑制患者的 TSO 治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/4f58bf913a3c/41598_2017_16287_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/05358f93a660/41598_2017_16287_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/1be1de82628b/41598_2017_16287_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/240c577adf89/41598_2017_16287_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/7e245059ed75/41598_2017_16287_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/9c2c3bb442ff/41598_2017_16287_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/4e45f6489c59/41598_2017_16287_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/1caac1141bdc/41598_2017_16287_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/3bb46d7c142d/41598_2017_16287_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/4f58bf913a3c/41598_2017_16287_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/05358f93a660/41598_2017_16287_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/1be1de82628b/41598_2017_16287_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/240c577adf89/41598_2017_16287_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/7e245059ed75/41598_2017_16287_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/9c2c3bb442ff/41598_2017_16287_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/4e45f6489c59/41598_2017_16287_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/1caac1141bdc/41598_2017_16287_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/3bb46d7c142d/41598_2017_16287_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6ae/5705695/4f58bf913a3c/41598_2017_16287_Fig9_HTML.jpg

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