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大肠杆菌O157:H7实验性感染对牛宿主的潜在免疫抑制作用。

Potential immunosuppressive effects of Escherichia coli O157:H7 experimental infection on the bovine host.

作者信息

Kieckens E, Rybarczyk J, Li R W, Vanrompay D, Cox E

机构信息

Laboratory of Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.

Laboratory of Immunology and Animal Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, 9000, Ghent, Belgium.

出版信息

BMC Genomics. 2016 Dec 21;17(1):1049. doi: 10.1186/s12864-016-3374-y.

Abstract

BACKGROUND

Enterohaemorrhagic Escherichia coli (EHEC), like E. coli O157:H7 are frequently detected in bovine faecal samples at slaughter. Cattle do not show clinical symptoms upon infection, but for humans the consequences after consuming contaminated beef can be severe. The immune response against EHEC in cattle cannot always clear the infection as persistent colonization and shedding in infected animals over a period of months often occurs. In previous infection trials, we observed a primary immune response after infection which was unable to protect cattle from re-infection. These results may reflect a suppression of certain immune pathways, making cattle more prone to persistent colonization after re-infection. To test this, RNA-Seq was used for transcriptome analysis of recto-anal junction tissue and ileal Peyer's patches in nine Holstein-Friesian calves in response to a primary and secondary Escherichia coli O157:H7 infection with the Shiga toxin (Stx) negative NCTC12900 strain. Non-infected calves served as controls.

RESULTS

In tissue of the recto-anal junction, only 15 genes were found to be significantly affected by a first infection compared to 1159 genes in the ileal Peyer's patches. Whereas, re-infection significantly changed the expression of 10 and 17 genes in the recto-anal junction tissue and the Peyer's patches, respectively. A significant downregulation of 69 immunostimulatory genes and a significant upregulation of seven immune suppressing genes was observed.

CONCLUSIONS

Although the recto-anal junction is a major site of colonization, this area does not seem to be modulated upon infection to the same extent as ileal Peyer's patches as the changes in gene expression were remarkably higher in the ileal Peyer's patches than in the recto-anal junction during a primary but not a secondary infection. We can conclude that the main effect on the transcriptome was immunosuppression by E. coli O157:H7 (Stx) due to an upregulation of immune suppressive effects (7/12 genes) or a downregulation of immunostimulatory effects (69/94 genes) in the ileal Peyer's patches. These data might indicate that a primary infection promotes a re-infection with EHEC by suppressing the immune function.

摘要

背景

肠出血性大肠杆菌(EHEC),如大肠杆菌O157:H7,在屠宰时的牛粪便样本中经常被检测到。牛感染后不表现出临床症状,但对人类而言,食用受污染牛肉后的后果可能很严重。牛对EHEC的免疫反应并不总能清除感染,因为感染动物通常会在数月内持续定植和排菌。在之前的感染试验中,我们观察到感染后的初次免疫反应无法保护牛免受再次感染。这些结果可能反映了某些免疫途径的抑制,使牛在再次感染后更容易发生持续定植。为了验证这一点,我们使用RNA测序对9头荷斯坦-弗里生犊牛的直肠肛门交界处组织和回肠派伊尔氏结进行转录组分析,以响应志贺毒素(Stx)阴性的NCTC12900菌株引起的初次和二次大肠杆菌O157:H7感染。未感染的犊牛作为对照。

结果

在直肠肛门交界处组织中,与初次感染相比,只有15个基因被发现受到显著影响,而在回肠派伊尔氏结中有1159个基因受到影响。然而,再次感染分别使直肠肛门交界处组织和派伊尔氏结中10个和17个基因的表达发生了显著变化。观察到69个免疫刺激基因显著下调,7个免疫抑制基因显著上调。

结论

尽管直肠肛门交界处是主要的定植部位,但该区域在感染时似乎没有像回肠派伊尔氏结那样受到同等程度的调节,因为在初次感染而非二次感染期间,回肠派伊尔氏结中的基因表达变化明显高于直肠肛门交界处。我们可以得出结论,对转录组的主要影响是大肠杆菌O157:H7(Stx)导致的免疫抑制,这是由于回肠派伊尔氏结中免疫抑制作用上调(7/12个基因)或免疫刺激作用下调(69/94个基因)。这些数据可能表明初次感染通过抑制免疫功能促进了EHEC的再次感染。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e52/5178093/55edea5ef6db/12864_2016_3374_Fig1_HTML.jpg

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