科學(xué)家發(fā)現(xiàn)了人體免疫系統(tǒng)對(duì)瘧疾和結(jié)核病感染做出響應(yīng)的一種方式，這提示人們可以用新的抗感染療法治療疾病,。
他們發(fā)現(xiàn),，人們有兩個(gè)不同版本的關(guān)鍵蛋白Mal，警告人體免疫系統(tǒng)有入侵細(xì)菌,。一種版本的蛋白讓免疫系統(tǒng)正常響應(yīng),，而另一種導(dǎo)致了過(guò)于強(qiáng)烈的反應(yīng)。該研究發(fā)表在了4月出版的《自然·遺傳學(xué)》雜志上,，它證明了兩種蛋白的不平衡可以讓一些人更容易患病,。
人體攜帶有兩種Mal蛋白，一種遺傳自母親,，另一種遺傳自父親,。攜帶有兩種不太活躍的Mal蛋白意味著人體不會(huì)對(duì)感染做出足夠的響應(yīng)，疾病將占上風(fēng),。而攜帶有兩種高度活躍的Mal蛋白意味著免疫系統(tǒng)過(guò)載,，導(dǎo)致嚴(yán)重的病情,。
英國(guó)Wellcome基金會(huì)人類遺傳學(xué)中心的Adrian Hill領(lǐng)導(dǎo)了這項(xiàng)研究，他告訴本網(wǎng)站說(shuō)： "擁有各自來(lái)源于父母的兩種版本的蛋白是最理想的,。這讓傳導(dǎo)的信號(hào)適中,，導(dǎo)致程度合適的炎癥反應(yīng)。"
該研究組說(shuō)可以開(kāi)發(fā)一種藥物調(diào)控Mal 蛋白的不平衡,。Hill說(shuō)： "我們的下一步是朝著開(kāi)發(fā)這種藥物努力,。"
這組科學(xué)家研究了來(lái)自阿爾及利亞、岡比亞,、幾內(nèi)亞比紹,、幾內(nèi)亞、肯尼亞,、英國(guó)和越南的感染細(xì)菌性肺炎,、血液細(xì)菌感染、瘧疾和結(jié)核病的6106患者,。
Wellcome基金會(huì)的負(fù)責(zé)人Mark Walport說(shuō)："特別是考慮到近來(lái)耐藥株病例數(shù)量的上升,，如果我們要開(kāi)發(fā)新的療法，理解免疫系統(tǒng)如何對(duì)感染做出響應(yīng)是至關(guān)重要的,。"
部分英文原文：
Nature Genetics - 39, 523 - 528 (2007)
Published online: 25 February 2007; | doi:10.1038/ng1976
A Mal functional variant is associated with protection against invasive pneumococcal disease, bacteremia, malaria and tuberculosis
Chiea C Khor1, 13, 14, Stephen J Chapman1, 2, 14, Fredrik O Vannberg1, Aisling Dunne3, Caroline Murphy3, Edmund Y Ling1, Angela J Frodsham1, Andrew J Walley1, 13, Otto Kyrieleis3, Amir Khan3, Christophe Aucan1, Shelley Segal4, Catrin E Moore4, Kyle Knox5, Sarah J Campbell1, Christian Lienhardt6, Anthony Scott7, Peter Aaby8, Oumou Y Sow9, Robert T Grignani1, 13, Jackson Sillah10, Giorgio Sirugo10, Nobert Peshu7, Thomas N Williams7, Kathryn Maitland7, Robert J O Davies2, Dominic P Kwiatkowski1, 4, 10, Nicholas P Day11, Djamel Yala12, Derrick W Crook4, Kevin Marsh7, James A Berkley7, Luke A J O'Neill3, 14 & Adrian V S Hill1, 14
1 The Wellcome Trust Centre for Human Genetics, University of Oxford, UK.
2 Osler Chest Unit, Churchill Hospital, Oxford, UK.
3 School of Biochemistry and Immunology, Trinity College, Dublin, Ireland.
4 Department of Paediatrics, John Radcliffe Hospital, Oxford, UK.
5 Department of Microbiology, John Radcliffe Hospital, Oxford, UK.
6 Institut de Recherche pour le Developpement, Dakar, Senegal.
7 Kenya Medical Research Institute/Wellcome Trust Programme, Centre for Geographic Medicine Research, Coast, Kilifi District Hospital, Kilifi, Kenya.
8 Bandim Health Project, Apartado 861, Bissau, Guinea-Bissau.
9 Service de Pneumo-Phtisiologie, University Ignace Deen, Conakry, BP 634, Republic of Guinea.
10 Medical Research Council Laboratories, Fajara, The Gambia.
11 Center for Tropical Diseases, Cho Quan Hospital, Ho Chi Minh City, Vietnam.
12 Service de la Tuberculose, Institut Pasteur d'Algérie, 2 rue du Dr Laveran Hamma, Algiers, Algeria.
13 Present addresses: Section of Genomic Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK (A.J.W.); Section for Genetic Medicine, Centre for Molecular Medicine, Agency for Science, Technology and Research, Singapore (C.C.K., R.T.G.).
14 These authors contributed equally to this work.
Correspondence should be addressed to Adrian V S Hill [email protected] or Luke A J O'Neill [email protected]
Toll-like receptors (TLRs) and members of their signaling pathway are important in the initiation of the innate immune response to a wide variety of pathogens1, 2, 3. The adaptor protein Mal (also known as TIRAP), encoded by TIRAP (MIM 606252), mediates downstream signaling of TLR2 and TLR4 (refs. 4–6). We report a case-control study of 6,106 individuals from the UK, Vietnam and several African countries with invasive pneumococcal disease, bacteremia, malaria and tuberculosis. We genotyped 33 SNPs, including rs8177374, which encodes a leucine substitution at Ser180 of Mal. We found that heterozygous carriage of this variant associated independently with all four infectious diseases in the different study populations. Combining the study groups, we found substantial support for a protective effect of S180L heterozygosity against these infectious diseases (N = 6,106; overall P = 9.6 10-8). We found that the Mal S180L variant attenuated TLR2 signal transduction.
