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蛋鸡斑点肝病的免疫反应与恢复

Immune responses and recovery from spotty liver disease in layer birds.

作者信息

Eastwood Sarah, Wilson Timothy B, Huang Jiongrui, Campbell Bronwyn E, Scott Peter C, Moore Robert J, Van Thi Thu Hao

机构信息

School of Science, RMIT University, Bundoora West Campus, Bundoora, Victoria, Australia.

Scolexia Pty Ltd., Moonee Ponds, Victoria, Australia.

出版信息

Poult Sci. 2025 May 26;104(8):105351. doi: 10.1016/j.psj.2025.105351.

DOI:10.1016/j.psj.2025.105351
PMID:40446677
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12166876/
Abstract

Spotty Liver Disease (SLD), caused by Campylobacter hepaticus, greatly impacts the health and egg production of affected layer hens and is a disease of concern in the poultry industry. This study aimed to enhance the understanding of the immune response in chickens to C. hepaticus infection and their ability to resist reinfections. One hundred- and twenty-layer chickens were allocated to 10 groups and challenged, from one to three times, with C. hepaticus HV10, with six weeks between each challenge. Blood and cloacal swabs were collected every three weeks to assess antibody responses and Campylobacter presence. Upon necropsy, bile, spleen, jejunum, and blood samples were collected for C. hepaticus detection and host gene expression analysis using qPCR and RNA sequencing. We found that most birds challenged with C. hepaticus for the second or third time did not develop liver lesions even with the presence of C. hepaticus in their bile, suggesting that birds were resistant to disease development following repeated exposure. Anti-C. hepaticus antibodies increased significantly six weeks after a single challenge but reduced from nine weeks. Quantitative PCR demonstrated that C. hepaticus could be recovered from the bile six weeks after a single challenge and increased significantly after a secondary challenge. RNA-seq and qPCR data demonstrate an elevation in pro-inflammatory cytokines, such as interleukin 6 (IL-6) and interleukin 1ß (IL-1ß), after a secondary challenge and down-regulation during a third challenge. Expression of many genes encoding barrier-supporting proteins genes were differentially expressed, with increased expression following a third challenge compared to expression after a single challenge. Comparison of gene expression in tissues of triple to a single challenged birds demonstrated that many genes involved in cytokine activity and the JAK-STAT cascade were down-regulated whereas other immune system pathways were up-regulated. Altogether, the results indicate that over time, immune memory, enhanced barrier function, and a balanced immune response developed, resulting in reduced impact of infection on the birds. These findings show that the impact of C. hepaticus infection can be ameliorated by immune responses and hence indicate that vaccines that induce appropriate protective immune responses should provide an effective tool to reduce SLD in poultry.

摘要

由肝弯曲杆菌引起的斑点状肝病(SLD)对受影响的蛋鸡的健康和产蛋量有很大影响,是家禽业关注的一种疾病。本研究旨在加深对鸡对肝弯曲杆菌感染的免疫反应及其抵抗再次感染能力的理解。将120只蛋鸡分为10组,用肝弯曲杆菌HV10进行1至3次攻毒,每次攻毒间隔6周。每3周采集血液和泄殖腔拭子,以评估抗体反应和弯曲杆菌的存在情况。剖检时,采集胆汁、脾脏、空肠和血液样本,用于通过qPCR和RNA测序检测肝弯曲杆菌并进行宿主基因表达分析。我们发现,大多数第二次或第三次受到肝弯曲杆菌攻毒的鸡即使胆汁中存在肝弯曲杆菌也未出现肝脏病变,这表明鸡在反复接触后对疾病发展具有抵抗力。抗肝弯曲杆菌抗体在单次攻毒6周后显著增加,但从9周后开始下降。定量PCR表明,单次攻毒6周后可从胆汁中检出肝弯曲杆菌,二次攻毒后显著增加。RNA测序和qPCR数据表明,二次攻毒后促炎细胞因子如白细胞介素6(IL-6)和白细胞介素1β(IL-1β)升高,第三次攻毒时下调。许多编码屏障支持蛋白基因的表达存在差异,与单次攻毒后的表达相比,第三次攻毒后表达增加。对三次攻毒鸡与单次攻毒鸡组织中的基因表达进行比较表明,许多参与细胞因子活性和JAK-STAT级联反应的基因下调,而其他免疫系统途径上调。总之,结果表明随着时间的推移,免疫记忆、增强的屏障功能和平衡的免疫反应得以发展,从而降低了感染对鸡的影响。这些发现表明,肝弯曲杆菌感染的影响可通过免疫反应得到改善,因此表明诱导适当保护性免疫反应的疫苗应提供一种有效的工具来减少家禽中的斑点状肝病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/29ed48631ad8/gr5.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/4a735ffa7af7/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/29ed48631ad8/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/bd4d0a0cea34/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/81b0093638b0/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/dc6c9b6d832e/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d426/12166876/4a735ffa7af7/gr4.jpg
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本文引用的文献

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Intestinal Colonization of and Its Hepatic Dissemination Are Associated with Local and Systemic Immune Responses in Broiler Chickens.肉鸡肠道定植及其肝脏播散与局部和全身免疫反应相关。
Microorganisms. 2023 Jun 28;11(7):1677. doi: 10.3390/microorganisms11071677.
2
Campylobacter bilis, the second novel Campylobacter species isolated from chickens with Spotty Liver Disease, can cause the disease.从患有斑点状肝病的鸡中分离出的第二种新型弯曲杆菌——胆汁弯曲杆菌,可引起该疾病。
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Enhancement of Campylobacter hepaticus culturing to facilitate downstream applications.
增强弯曲杆菌属(Campylobacter hepaticus)的培养以促进下游应用。
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Isoquinoline alkaloids induce partial protection of laying hens from the impact of Campylobacter hepaticus (spotty liver disease) challenge.异喹啉生物碱可诱导产蛋母鸡对弯曲杆菌(点状肝病)感染的部分保护。
Poult Sci. 2021 Nov;100(11):101423. doi: 10.1016/j.psj.2021.101423. Epub 2021 Aug 9.
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Development of an enzyme-linked immunosorbent assay for detecting specific antibodies in chicken sera - a key tool in Spotty Liver Disease screening and vaccine development.建立酶联免疫吸附试验检测鸡血清中特异性抗体的方法——用于斑点肝脏病筛查和疫苗开发的关键工具。
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