據(jù)4月23日的《科學(xué)》雜志報(bào)道,，研究人員發(fā)現(xiàn),，在感染HIV的非洲成年人中的一種有缺陷的免疫反應(yīng)使得他們特別容易感染某些沙門氏桿菌的菌株。他們的發(fā)現(xiàn)可幫助解釋為什么HIV患者會(huì)因?yàn)檫@種條件致病菌而造成如此高的死亡率,。他們的結(jié)果可能還可以使人們?cè)谖磥砩a(chǎn)出更為有效的針對(duì)HIV的疫苗,，這些疫苗還可保護(hù)人們不受沙門氏菌的感染。Calman MacLennan及其同僚曾經(jīng)估計(jì),，受到HIV感染的患者可能較難產(chǎn)生針對(duì)沙門氏菌的特異性抗體,。
但他們所發(fā)現(xiàn)的正好與其估計(jì)的情況相反：在感染HIV的患者中，針對(duì)該細(xì)菌的脂多糖（或稱LPS,，這是細(xì)菌細(xì)胞壁中的蛋白）的特異性抗體的濃度是增加的,。（在具有健康免疫反應(yīng)的患者中，其產(chǎn)生的特異性抗體是針對(duì)細(xì)菌的外側(cè)膜蛋白的,，這些抗體可成功地殺滅沙門氏菌并清除感染,。）研究人員接著發(fā)現(xiàn)，HIV感染的血清仍然可以殺滅缺乏LPS的沙門氏菌株,，而將HIV感染的血清中清除掉LPS特異性的抗體可使得該血清重新具有抗沙門氏菌的功效,。他們的發(fā)現(xiàn)意味著HIV所造成的缺陷不止是細(xì)胞介導(dǎo)的免疫，而體液免疫（是由分泌的抗體所介導(dǎo)的）在以LPS蛋白為標(biāo)靶的免疫反應(yīng)中也受到了相當(dāng)大的損害,。
這一缺損的免疫反應(yīng)在HIV感染的患者中具有嚴(yán)重的后果,，尤其是當(dāng)其面臨繼發(fā)性感染的時(shí)候,。研究人員提示，未來的疫苗應(yīng)該將該沙門氏菌的外側(cè)膜作為標(biāo)靶,，而不是以LPS作為標(biāo)靶,。在一則Perspective中，Susan Moir 和 Anthony Fauci更為詳細(xì)地解釋了這些發(fā)現(xiàn)以及它們的含意,。(生物谷Bioon.com)
生物谷推薦原文出處：
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.
