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Science:艾滋病患者易患沙门氏菌感染原因

2010/4/24 17:08:26


    据4月23日的《科学》杂志报道,研究人员发现,在感染HIV的非洲成年人中的一种有缺陷的免疫反应使得他们特别容易感染某些沙门氏杆菌的菌株。他们的发现可帮助解释为什么HIV患者会因为这种条件致病菌而造成如此高的死亡率。他们的结果可能还可以使人们在未来生产出更为有效的针对HIV的疫苗,这些疫苗还可保护人们不受沙门氏菌的感染。Calman MacLennan及其同僚曾经估计,受到HIV感染的患者可能较难产生针对沙门氏菌的特异性抗体。

  但他们所发现的正好与其估计的情况相反:在感染HIV的患者中,针对该细菌的脂多糖(或称LPS,这是细菌细胞壁中的蛋白)的特异性抗体的浓度是增加的。(在具有健康免疫反应的患者中,其产生的特异性抗体是针对细菌的外侧膜蛋白的,这些抗体可成功地杀灭沙门氏菌并清除感染。)研究人员接着发现,HIV感染的血清仍然可以杀灭缺乏LPS的沙门氏菌株,而将HIV感染的血清中清除掉LPS特异性的抗体可使得该血清重新具有抗沙门氏菌的功效。他们的发现意味着HIV所造成的缺陷不止是细胞介导的免疫,而体液免疫(是由分泌的抗体所介导的)在以LPS蛋白为标靶的免疫反应中也受到了相当大的损害。

  这一缺损的免疫反应在HIV感染的患者中具有严重的后果,尤其是当其面临继发性感染的时候。研究人员提示,未来的疫苗应该将该沙门氏菌的外侧膜作为标靶,而不是以LPS作为标靶。在一则Perspective中,Susan Moir 和 Anthony Fauci更为详细地解释了这些发现以及它们的含意。

生物谷推荐原文出处:

Science   DOI: 10.1126/science.1180346

Dysregulated Humoral Immunity to Nontyphoidal Salmonella in HIV-Infected African Adults
Calman A. MacLennan,1,4,* James J. Gilchrist,1,2,5 Melita A. Gordon,2,6,7 Adam F. Cunningham,1 Mark Cobbold,1 Margaret Goodall,1 Robert A. Kingsley,8 Joep J. G. van Oosterhout,2,7 Chisomo L. Msefula,2,4,9 Wilson L. Mandala,2,9,10 Denisse L. Leyton,11 Jennifer L. Marshall,1 Esther N. Gondwe,1,2,9 Saeeda Bobat,1 Constantino López-Macías,12 Rainer Doffinger,13 Ian R. Henderson,11 Eduard E. Zijlstra,7 Gordon Dougan,8 Mark T. Drayson,1 Ian C. M. MacLennan,1 Malcolm E. Molyneux2,7,9

Nontyphoidal Salmonellae are a major cause of life-threatening bacteremia among HIV-infected individuals. Although cell-mediated immunity controls intracellular infection, antibodies protect against Salmonella bacteremia. We report that high-titer antibodies specific for Salmonella lipopolysaccharide (LPS) are associated with a lack of Salmonella-killing in HIV-infected African adults. Killing was restored by genetically shortening LPS from the target Salmonella or removing LPS-specific antibodies from serum. Complement-mediated killing of Salmonella by healthy serum is shown to be induced specifically by antibodies against outer membrane proteins. This killing is lost when excess antibody against Salmonella LPS is added. Thus, our study indicates that impaired immunity against nontyphoidal Salmonella bacteremia in HIV infection results from excess inhibitory antibodies against Salmonella LPS, whereas serum killing of Salmonella is induced by antibodies against outer membrane proteins.

1 Medical Research Council Centre for Immune Regulation and Clinical Immunology Service, Institute of Biomedical Research, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
2 Malawi—Liverpool—Wellcome Trust Clinical Research Programme, College of Medicine, University of Malawi, Blantyre, Malawi.
3 Division of Medical Microbiology, University of Liverpool, Liverpool, UK.
4 Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi.
5 Oxford University Clinical Academic Graduate School, Medical Sciences Division, John Radcliffe Hospital, Oxford, UK.
6 Gastroenterology Unit, University of Liverpool, Liverpool, UK.
7 Department of Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
8 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK.
9 Liverpool School of Tropical Medicine, Pembroke Place, University of Liverpool, Liverpool, UK.
10 Department of Biochemistry, College of Medicine, University of Malawi, Blantyre, Malawi.
11 Biosciences, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
12 Medical Research Unit on Immunochemistry, Specialties Hospital, National Medical Centre "Siglo XXI," Mexican Institute for Social Security, Mexico City, Mexico.
13 Department of Clinical Biochemistry and Immunology, Addenbrooke’s Hospital, Cambridge, UK.


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