近日，來自愛丁堡大學的研究人員通過研究揭示了感染性蛋白如何引發疾病擴散到大腦，這或可幫助對致死性大腦疾病的患者進行診斷，相關研究發表於國際雜誌Journal of Virology上。文章中研究者表示，個體在食用被感染性蛋白—朊病毒汙染的食物後，朊病毒就會通過腸道侵入到個體大腦，該研究或將幫助對朊病毒疾病的診斷，朊病毒疾病包括克雅二氏症及瘋牛病等。
早在20年前這種疾病非常罕見，當時229名患者死於克雅二氏症，朊病毒是一種具有異常形狀的感染性蛋白，其可以通過食用汙染的肉類在人群和動物之間傳播，截止到目前為止研究者尚不清楚朊病毒通過腸道侵襲到大腦中的分子機製。
這項研究中研究者就朊病毒如何在小鼠機體中通過腸道入侵到大腦中進行了詳盡的研究，研究者發現，朊病毒在擴散到大腦之前必須在小腸內壁建立自身特殊的結構，而腸道內壁一種名為淋巴集結的特殊結構是機體的部分免疫係統，而且可以形成機體對於汙染食物的第一道防線，朊病毒就會攔截淋巴集結來引發感染。
在後期感染階段朊病毒並不會在大腸內壁建立類似於補丁樣的斑塊結構，在此階段朊病毒可以在淋巴結和脾髒中被檢測到。據最新估計在英國大約有2000感染朊病毒的患者，但這些患者並沒有表現出任何症狀，在常規的闌尾切除手術中研究者對來自其機體的組織進行了分析。
研究者表示，我們的估測或許並不能鑒別出處於早期感染階段的患者，而處於早期階段朊病毒並不會越過小腸進行感染；當朊病毒進入大腦後，其就會破壞神經細胞引發一係列神經病變，比如記憶缺失、人格改變甚至移動困難。
最後研究者Neil Mabbott說道，是否所有個體通過腸道朊病毒感染繼而發展為神經係統疾病我們不得而知，後期我們還需要進行更多的研究來尋找是什麼因子可以增強機體對朊病毒的一感染，這對於研究朊病毒的致病機製及開發保護性措施或療法來抑製朊病毒疾病提供了新的思路和希望。
doi:10.1128/JVI.01544-15
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Thegut-associated lymphoid tissues in the small intestine, not the large intestine, play a major role in oralpriondisease pathogenesis
David S. Donaldsona, Kathryn J. Elseb and Neil A. Mabbotta#
Prion diseases are infectious neurodegenerative disorders characterised by accumulations of abnormally folded cellular prion protein in affected tissues. Many natural prion diseases are acquired orally and following exposure the early replication of some prion isolates upon follicular dendritic cells (FDC) within gut-associated lymphoid tissues (GALT) is important for the efficient spread of disease to the brain (neuroinvasion). Prion detection within large intestinal GALT biopsies has been used to estimate human and animal disease prevalence. However, the relative contributions of the small and large intestinal GALT to oral prion pathogenesis were unknown. To address this issue we created mice that specifically lacked FDC-containing GALT only in the small intestine. Our data show that oral prion disease susceptibility was dramatically reduced in mice lacking small intestinal GALT. Although these mice had FDC-containing GALT throughout their large intestines, these tissues were not early sites of prion accumulation or neuroinvasion. We also determined whether pathology specifically within the large intestine might influence prion pathogenesis. Congruent infection with the nematode parasite Trichuris muris in the large intestine around the time of oral prion exposure did not affect disease pathogenesis. Together, these data demonstrate that the small intestinal GALT are the major early sites of prion accumulation and neuroinvasion after oral exposure. This has important implications for our understanding of the factors that influence the risk to infection and the pre-clinical diagnosis of disease.
