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

Suzanne G St Rose,Louise Matthews,James D Foster,Nora Hunter,Darren J Shaw,Margo E Chase-Topping,Robert G Will,Mark Ej Woolhouse,Loeske Eb Kruuk,Susan M Rhind

doi:10.1186/1471-2334-6-5

Abstract

BackgroundEpidemiological 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.MethodsUsing 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, rs, between available measures of Peyer's patch (PP) development and the estimated risk of infection for an individual of the corresponding age.ResultsThere 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, rs = 0.913 (n = 19, P < 0.001), and lymphoid follicle density vs risk of infection, rs = 0.933 (n = 19, P < 0.001); for cattle, weight of PP tissue vs risk of infection, rs = 0.693 (n = 94, P < 0.001); and for humans, number of PPs vs risk of infection, rs = 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: rs = 0.360 (n = 46, P = 0.014).ConclusionOur 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.

Highlights

Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, the underlying mechanisms remain poorly understood
The incidence of natural cases of transmissible spongiform encephalopathies (TSEs) or prion diseases is related to age: scrapie incidence in sheep typically peaks between 2 and 3 years of age [1], bovine spongiform encephalopathy (BSE) incidence in cattle peaks at around 5 to 7 years of age [2] and variant Creutzfeldt-Jakob disease incidence in humans peaks at 25 to 30 years [3]
Peyer's patch (PP) tissue and lymphoid follicles were visualised by immersing the intestines in 2% acetic acid for 24 hours, and the follicular content of the patches enhanced by staining with 0.5% methylene blue for 2–5 minutes

Summary

Introduction

Epidemiological analyses indicate that the age distribution of natural cases of transmissible spongiform encephalopathies (TSEs) reflect age-related risk of infection, the underlying mechanisms remain poorly understood. Analyses of epidemiological data for scrapie [4], BSE [5] and vCJD [6] have suggested that there is significant age dependency in the risk of infection for all these TSEs. Available evidence suggests that these patterns cannot be fully accounted for by changes in exposure, in which case changes in susceptibility must play a role. Mice deficient in both tumour necrosis factor and lymphotoxin or in lymphocytes, in which PPs are decreased in number, are highly resistant to oral challenge and their intestines are virtually devoid of infectivity at all times post-challenge [11].

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