知之甚少的细胞在抵抗流感的免疫中起作用

新的研究可以指导创造有针对性的，更有效的疫苗

2010年3月21日

波士顿，大众。•在免疫系统中的某些细胞的新的理解可能有助于引导科学家在创造更好的流感疫苗，报告研究人员从程序在细胞和分子医学和免疫疾病研究所波士顿儿童医院(PCMM/IDI)。 Reporting online March 21 in Nature Immunology， they show， for the first time， that white blood cells known as resident dendritic cells (DCs) capture 流感 viruses and show them to B-lymphocytes， another white blood cell that recognizes germs and launches an antibody attack。 Harnessing this previously unknown function could help activate the immune system more effectively against the 流感 virus。

“政府投入大量资金，为疫苗的发展，说：”高级研究员米迦勒卡罗尔，博士，高级研究员和主任PCMM\/IDI的免疫学研究生课程号。”很多人都在思考如何目标疫苗，这种信息会告诉我们什么细胞类型，我们将要目标。

Carroll's lab， in collaboration with Shannon Turley of the Department of Cancer Immunology and AIDS at Dana Farber Cancer Institute and Department of Pathology， Harvard Medical School， closely examined what happens when a 流感 vaccine is injected into mice， a good model for human vaccination。 They focused specifically on what happens in the lymph node， where germs and vaccine antigens are filtered。

卡罗尔说：“我们试图打破这个黑盒子，我们知道作为淋巴结，并确定不同的细胞，它们是如何相互作用的，什么是一般规则，”说。然后，你可以开始操纵它来提高疫苗和免疫反应。”

When it comes to building permanent immunity， B-lymphocytes are the key players because they can remember specific germs and mount a rapid antibody attack。 One way B-lymphocytes first encounter germs in the lymph nodes is through the help of macrophages， white blood cells that trap germs and "show" them to B-lymphocytes。 For this reason， some researchers believe macrophages to be a prime target in developing a vaccine。 Carroll's lab designed their experiment to test this concept for the 流感 virus - and got surprising results。

Working with a mouse model of in流感enza vaccination， the lab attached 流感orescent labels to an inactivated strain of human H1N1 virus， allowing the inactivated 流感 virus to be tracked in the body。 Imaging showed that macrophages trapped the virus in the lymph nodes and prevented most of it from entering the circulation。 However， the macrophages did not bring the virus to B-lymphocytes， contrary to what was predicted。 Instead， experiments which eliminated the macrophages from the mouse models showed that it was actually the resident DCs in the lymph nodes that were bringing the 流感 virus to the B-lymphocytes， thus inducing the B-lymphocytes to launch an antibody attack。

To confirm this observation， the researchers injected the mice with an agent to block a specific receptor on the surface of the resident DCs。 With this receptor blocked， the B-lymphocytes never sprang into action。 When it comes to the 流感 virus， these results suggest that any targeted vaccine must aim for resident DCs and not macrophages。

“这是第一个明确的定义，居民的议会正在做什么，”卡罗尔说。这项研究增加了以树突状细胞为中心的研究机构，其研究还表明在刺激免疫系统中的其他细胞中发挥作用。

Targeting in流感enza vaccines to DCs could make them more effective， Carroll believes。 One hypothetical way of doing this would be to attach the virus to an antibody that would home in on the DC cell surface receptor。 This method would require further research to confirm the antibody could actually bind to the DC receptor。

在未来，卡罗尔的实验室想定义一个类似的免疫系统的途径，肺炎链球菌，一种细菌，可以导致疾病，如肺炎，脑膜炎中耳感染。

这一研究得到了国家卫生研究院的资助。第一作者圣地亚哥冈萨雷斯pcmmm \/公司由玛丽居里即将离任的国际职业发展奖学金支持。

引文：Santiago F。 Gonzalez， Veronika Lukacs-Kornek， Michael P。 Kuligowski， Lisa A。 Pitcher， Søren E。 Degn， Young-A Kim， Mary Cloninger， Luisa Martinez-Pomares， Siamon Gordon， Shannon J。 Turley & Michael C。 Carroll。 "Capture of in流感enza by medullary dendritic cells via SIGN-R1 is essential for humoral immunity in draining lymph nodes。" Nature Immunology March 21 (advanced online publication)。

接触：
艾琳的长跑冠军
617-919-3110
erin。mccolgan@childrens。harvard。edu

波士顿儿童医院 is home to the world's largest research enterprise based at a pediatric medical center， where its discoveries have benefited both children and adults since 1869。 More than 500 scientists， including eight members of the National Academy of Sciences， 11 members of the Institute of Medicine and 13 members of the Howard Hughes Medical Institute comprise Children's research community。 Founded as a 20-bed hospital for children， 波士顿儿童医院 today is a 397-bed comprehensive center for pediatric and adolescent health care grounded in the values of excellence in patient care and sensitivity to the complex needs and diversity of children and families。 Children's also is the primary pediatric teaching affiliate of Harvard Medical School。 For more information about the hospital and its research visit:www。childrenshospital。org\/newsroom。

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