报告题目：Immune cell-mediated inflammation and adhesion controls infectious diseases

报告人：王红艳  研究员

主持人： 王平 教授

报告时间：6月11日 13:30

报告地点：闵行生科院534报告厅

 

报告人简介：王红艳，研究员，研究组长，博士生导师。1993-1998 年安徽医科大学临床医学系本科；1998-2001 年安徽医科大学免疫系和中国预防医学科学院病毒所基因工程国家重点实验室联合培养硕士；2001-2006 英国伦敦帝国理工学院(Imperial College London) 博士及Research Associate； 2006-2010 英国剑桥大学Research Fellow；2010年3月任上海生化与细胞所研究员，研究组长；2011年入选中国科学院百人计划及上海市浦江人才计划。

 

报告摘要：Immune cell-mediated inflammation is involved in various infectious diseases. (1) TLR4 on macrophages plays key role against bacterial infection. After screening over 40 cytokines and receptors in LPS or bacterial-infected macrophages, we identified a significant increase of vascular endothelial growth factor receptors (VEGFR3) and its ligand VEGF-C. Using mouse models carrying the ligand-binding domain deletion of VEGFR3, we demonstrated in vitro and in vivo that VEGFR3 ligation by VEGF-C down-regulates TLR4-mediated NF-kB activation, inflammatory response and avoid septic shock. This study suggests that VEGFR3/VEGF-C signaling represents a novel ‘self-control’ mechanism during anti-bacterial innate immunity; Except for targeting lymphatic vessels, VEGFR3 also inhibits macrophage-mediated excessive inflammation, which explains why VEGFR3 mutant lymphedema patients are complicated with infections. We also suggest VEGF-C as a potential diagnosis marker for septic shock (IMMUNITY, 2014 April issue, Cover Story). (2) We previously identified that the T-cell adaptor protein ADAP (adhesion and degranulation-promoting adaptor protein) mediates T-cell adhesion and proliferation. Despite this, a connection between ADAP and HIV-1 infection has not been explored. We found that ADAP was needed for NF-κB-induced transcription of the HIV-1 in cooperation the co-receptor CD28, but not LFA-1. Furthermore, ADAP cooperated with LFA-1 to regulate virological synapse formation and viral spread between between T-dendritic cells. These findings indicate that ADAP regulates two steps of HIV-1 infection cooperatively with two distinct receptors, which might serve as a new potential target in the blockade of HIV-1 infection (RETROVIROLOGY, 2013).