科学家发现了人体免疫系统对疟疾和结核病感染做出响应的一种方式，这提示人们可以用新的抗感染疗法治疗疾病。
他们发现，人们有两个不同版本的关键蛋白Mal，警告人体免疫系统有入侵细菌。一种版本的蛋白让免疫系统正常响应，而另一种导致了过于强烈的反应。该研究发表在了4月出版的《自然·遗传学》杂志上，它证明了两种蛋白的不平衡可以让一些人更容易患病。
人体携带有两种Mal蛋白，一种遗传自母亲，另一种遗传自父亲。携带有两种不太活跃的Mal蛋白意味着人体不会对感染做出足够的响应，疾病将占上风。而携带有两种高度活跃的Mal蛋白意味着免疫系统过载，导致严重的病情。
英国Wellcome基金会人类遗传学中心的Adrian Hill领导了这项研究，他告诉本网站说： "拥有各自来源于父母的两种版本的蛋白是最理想的。这让传导的信号适中，导致程度合适的炎症反应。"
该研究组说可以开发一种药物调控Mal 蛋白的不平衡。Hill说： "我们的下一步是朝着开发这种药物努力。"
这组科学家研究了来自阿尔及利亚、冈比亚、几内亚比绍、几内亚、肯尼亚、英国和越南的感染细菌性肺炎、血液细菌感染、疟疾和结核病的6106患者。
Wellcome基金会的负责人Mark Walport说："特别是考虑到近来耐药株病例数量的上升，如果我们要开发新的疗法，理解免疫系统如何对感染做出响应是至关重要的。"
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 adrian.hill@well.ox.ac.uk or Luke A J O'Neill laoneill@tcd.ie
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.
