파이어스 패치(Peyer’s patch)와 프리온 질병의 연관성에 대한  2006년 [BMC Infectious

Diseases]에 발표된 논문입니다.

Comparative evidence for a link between Peyer’s patch development and susceptibility to transmissible spongiform encephalopathies

출처 : BMC Infectious Diseases 2006, 6:5doi:10.1186/1471-2334-6-5

http://www.biomedcentral.com/1471-2334/6/5/

Abstract

Background

Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, however, the underlying mechanisms remain poorly understood. Using a comparative approach, we tested the hypothesis that, there is a significant correlation between risk of infection for scrapie, bovine spongiform encephalopathy (BSE) and variant CJD (vCJD), and the development of lymphoid tissue in the gut.

Methods

Using anatomical data and estimates of risk of infection in mathematical models (which included results from previously published studies) for sheep, cattle and humans, we calculated the Spearman’s rank correlation coefficient, r_s, between available measures of Peyer’s patch (PP) development and the estimated risk of infection for an individual of the corresponding age.

Results

There was a significant correlation between the measures of PP development and the estimated risk of TSE infection; the two age-related distributions peaked in the same age groups. This result was obtained for each of the three host species: for sheep, surface area of ileal PP tissue vs risk of infection, r_s = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, r_s = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, r_s = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, r_s = 0.384 (n = 46, P = 0.008). In addition, when changes in exposure associated with BSE-contaminated meat were accounted for, the two age-related patterns for humans remained concordant: r_s = 0.360 (n = 46, P = 0.014).

Conclusion

Our findings suggest that, for sheep, cattle and humans alike there is an association between PP development (or a correlate of PP development) and susceptibility to natural TSE infection. This association may explain changes in susceptibility with host age, and differences in the age-susceptibility relationship between host species.

수학적 모델을 사용하여 젊은 사람들이 인간광우병( vCJD)에 보다 취약한 역학적 증거를

Pierre-Yves Boëlle 등이 2004년 [BMC Infectious Diseases]에 발표한 논문입니다.

Pierre-Yves Boëlle¹ , Jean-Yves Cesbron² and Alain-Jacques Valleron¹

¹  INSERM U444, Assistance Publique Hôpitaux de Paris, Université Pierre et Marie Curie, Paris, France

²  Immunité Anti-Infectieuse JE 2236, UFR de Médecine de Grenoble, Université Joseph Fourier, Grenoble, France

http://www.biomedcentral.com/1471-2334/4/26
 

Abstract

Background

The strikingly young age of new variant Creutzfeldt-Jacob disease (vCJD) cases remains unexplained. Age dependent susceptibility to infection has been put forward, but differential dietary exposure to contaminated food products in the UK population according to age and sex during the bovine spongiform encephalopathy (BSE) epidemic may provide a simpler explanation.

Methods

Using recently published estimates of dietary exposure in mathematical models of the epidemiology of the new variant Creutzfeldt Jacob disease (vCJD), we examine whether the age characteristics of vCJD cases may be reproduced.

Results

The susceptibility/exposure risk function has likely peaked in adolescents and was followed by a sharp decrease with age, evocative of the profile of exposure to bovine material consumption according to age. However, assuming that the risk of contamination was proportional to exposure, with no age dependent susceptibility, the model failed to reproduce the observed age characteristics of the vCJD cases: The predicted cumulated proportion of cases over 40 years was 48%, in strong disagreement with the observed 10%. Incorporating age dependent susceptibility led to a cumulated proportion of cases over 40 years old of 12%.

Conclusions

This analysis provides evidence that differential dietary exposure alone fails to explain the pattern of age in vCJD cases. Decreasing age related susceptibility is required to reproduce the characteristics of the age distribution of vCJD cases.

신경세포 뉴런으로 프리온이 이동하는데 있어서 수지상 세포(dendritic cells)의 역할에 대한 특징에 대한 2010년 7월에 발표된 논문입니다. 출처를 클릭하시면 논문의 전문을 볼 수 있습니다.

Characterization of the role of dendritic cells in prion transfer to primary neurons

Langevin Christelle1, Gousset Karine1, Costanzo Maddalena1, Odile Richard Le Goff1, Zurzolo Chiara1,2, *.

출처 : Biochemical Journal Immediate Publication. Published on 30 Jul 2010 as manuscript BJ20100698

 

로슬린연구소의 연구자들은 쥐 실험을 통해 나이에 따른 소포성 수지상 세포 (follicular dendritic cells)와 프리온 단백질의 상호작용에 대한 연구결과를 발표했습니다.

변형 프리온은 중추신경계로 퍼지기 전에 비장, 림파구, 편도 등 면역계의 일부인 림프조직에 축적되는데, Neil Mabbott를 비롯한 로슬린 연구소의 학자들은 프리온은 필수불가결하게 면역계의 특별한 세포인 소포성 수지상 세포 (follicular dendritic cells)를  “납치(hijack)”하는 것을 확인했습니다.(변형 프리온 단백질이 소포성 수지상 세포와 반드시 결합하여 그 세포에서 축적되고 복제됩니다)

그러나 나이 든 쥐에서는 소포성 수지상 세포가 손상된(감소된) 것이 확인됐습니다.

광우병과 소포성 수지상 세포 (follicular dendritic cells)의 연관성은 예전에 [네이처]에도 발표된 바가 있습니다.

논문의 영문 요약문과 출처는 아래와 같습니다.

 

=================================================

The Effects of Host Age on Follicular Dendritic Cell Status Dramatically Impair Scrapie Agent Neuroinvasion in Aged Mice¹

Karen L. Brown,^2* Gwennaelle J. Wathne,^* Jill Sales, Moira E. Bruce,^* and Neil A. Mabbott^2*

^*The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Roslin, United Kingdom; and Biomathematics & Statistics Scotland, Edinburgh, United Kingdom

출처 : Published online September 28, 2009
The Journal of Immunology, 2009, 183, 5199 -5207
http://www.jimmunol.org/cgi/content/abstract/183/8/5199
doi:10.4049/jimmunol.0802695

Following peripheral exposure, many transmissible spongiform encephalopathy (TSE) agents accumulate first in lymphoid tissues before spreading to the CNS (termed neuroinvasion) where they cause neurodegeneration. Early TSE agent accumulation upon follicular dendritic cells (FDCs) in lymphoid follicles appears critical for efficient neuroinvasion. Most clinical cases of variant Creutzfeldt-Jakob disease have occurred in young adults, although the reasons behind this apparent age-related susceptibility are uncertain. Host age has a significant influence on immune function. As FDC status and immune complex trapping is reduced in aged mice (600 days old), we hypothesized that this aging-related decline in FDC function might impair TSE pathogenesis. We show that coincident with the effects of host age on FDC status, the early TSE agent accumulation in the spleens of aged mice was significantly impaired. Furthermore, following peripheral exposure, none of the aged mice developed clinical TSE disease during their lifespans, although most mice displayed histopathological signs of TSE disease in their brains. Our data imply that the reduced status of FDCs in aged mice significantly impairs the early TSE agent accumulation in lymphoid tissues and subsequent neuroinvasion. Furthermore, the inefficient neuroinvasion in aged individuals may lead to significant levels of subclinical TSE disease in the population.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by funding from the European Commission, UK Biotechnology and Biological Sciences Research Council, and the Medical Research Council.

² Address correspondence and reprint requests to Dr. Karen L. Brown and Dr. Neil A. Mabbott, The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Roslin, Midlothian EH25 9PS, U.K. E-mail: karen.brown@roslin.ed.ac.uk and neil.mabbott@roslin.ed.ac.uk

³ Abbreviations used in this paper: TSE, transmissible spongiform encephalopathy; FDC, follicular dendritic cell; PrP, prion protein; vCJD, variant Creutzfeldt-Jakob disease; BSE, bovine spongiform encephalopathy; CR, complement receptor; i.c., intracerebral; TH, tyrosine hydroxylase; PK, proteinase K.

⁴ The online version of this article contains supplemental material.

^{================================}

Dr Neil Mabbott

neil.mabbott@roslin.ed.ac.uk

Identification of critical cells and molecules involved in the delivery of TSE agents from the site of infection to the brain.

출처 : http://www.roslin.ac.uk/research/people.php/Neil.Mabbott

Contact Details

Dr Neil Mabbott
Group Leader
Neuropathogenesis Division

The Roslin Institute and R(D)SVS, University of Edinburgh
Roslin Biocentre
Roslin Institute
Midlothian
EH25 9PS

Tel: 0131 527 4200
Fax: 0131 440 0434

e-mail: neil.mabbott@roslin.ed.ac.uk

 

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T09-4Y29SSG-3&_user=10&_coverDate=12%2F31%2F2009&_rdoc=1&_fmt=high&_orig=search&_origin=search&_sort=d&_docanchor=&view=c&_searchStrId=1454112623&_rerunOrigin=google&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ae4e0902e4a5403eb5748b5a012c9c99&searchtype=a

1.

Introduction

2.

Materials and methods

2.1. Animal study

2.2. Histology and immunohistochemistry

2.3. Preparation of brain homogenates

2.4. Immunoblotting

2.5. Real-time PCR

2.6. Statistical analysis

3.

Results

3.1. Extended incubation time of prion disease in mice infected at old age

3.2. Milder neuropathology of prion disease in mice infected at older age

3.3. Decreased accumulation of PrP^Sc in the brains and spleens of aged mice

3.4. Elevated PrP^C protein levels in the brains of normal aged mice

3.5. Spleens of aged and young naïve mice present comparable mRNA levels of tyrosine hydroxylase (TH)

3.6. The effect of age on the upregulation of disease-associated genes in response to prion infection

4.

Discussion

Conflict of statement

References