Gr-1+MDSC样细胞在宿主抗衣原体呼吸道感染中的作用及作用机制

项目名称： Gr-1+MDSC样细胞在宿主抗衣原体呼吸道感染中的作用及作用机制

项目编号： No.81501761

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 赵蕾

作者单位： 山东大学

项目金额： 18万元

中文摘要： 衣原体感染伴随感染部位Gr-1+细胞大量浸润。目前关于Gr-1+细胞在宿主抗衣原体感染中作用的研究尚存在很多争议。Gr-1+细胞如何调控宿主抗衣原体免疫应答的机制也知之甚少。本课题组前期工作发现，衣原体感染诱导的Gr-1+细胞可分解为Gr-1hi和Gr-1int亚群，且Gr-1+细胞亚群构成的差异与C3H小鼠抗衣原体感染易感性的增加有关。结合近年来急慢性感染中髓系抑制细胞聚集及亚群功能研究的相关文献，我们猜测，衣原体感染可诱导Gr-1+MDSC样免疫抑制细胞在感染部位(和/或淋巴组织)的聚集，该细胞通过调节宿主抗衣原体免疫应答导致不同的感染结局。本课题将从解析Gr-1+细胞亚群构成的全新角度，阐明Gr-1+ MDSC样细胞在宿主抵抗衣原体感染中的作用及其作用机制。本研究将为揭示衣原体感染诱导的Gr-1+ MDSC样免疫抑制细胞的作用及作用机制奠定基础，并为衣原体感染的防治提供新的理论依据

中文关键词： 衣原体；中性粒细胞；髓系细胞；固有免疫

英文摘要： Chlamydia infection is a serious public-health problem worldwide. So far, no vaccine is available to prevent human chlamydial dieases due to the lack of clear understanding of immune mechanisms to chlamydial infections. Chlamydial infection is accompanied by significant infiltration of neutrophils at the site of infection. It has been reported that neutrophils are able to destroy chlamydiae in vitro. However, the in vivo role of PMNs in host defense against C. muridarum infection is still controversial, and the underlying mechanisms by which PMNs cells modulate immune response during C. muridarum infection is largely unknown. Our preliminary experiment showed that the Gr-1+ cells accumulating during infection can be divided into Gr-1hi and Gr-1int subpopulations. The percentage of each subset are significantly different between a resistant strain C57BL/6 mice and a susceptible strain C3H/HeN mice following C. muridarum infection. To date , studies identify the influx of neutrophils based on simply measuring “Gr1-positive” cells, but clearly our current concept needs to be significantly modified because Gr-1 Ab RB6-C85 recognizes both Ly6G and Ly6C epitopes. Based on the observation that higher neutrophil infiltration is not always associated with better protection, and they share surface markers with MDSC，we assume that Chlamydia infection induce Gr-1+ MDSC-like cell accumulation at infect site AND/OR in the peripheral lymphoid tissues, which affect host sensibility to C. muridarum infection though turnning off the effective innate and adaptive immune response. On the basis of this hypothesis , in present study, we will explore the accumulation kinetics of Gr-1+ cell as well as its major subsets during C. muridarum lung infection and identify the morphologic, phenotypic and functional characteristics. Furthermore, By combining two different antibody blocking approaches and cell adoptive transfer strategy, we aim to determine the role of Gr-1+ cell in host defense against Chlamydia lung infection and to elucidate the mechanisms by which Gr-1+ cell influence host resistance to chlamydial lung infection. This study will gain insight on a better understanding of the defence mechanism to chlamydial infection, which has significant implications in chlamydial vaccine development and designing strategies.

英文关键词： chlamydia;nuetrophil;myeloid cell;innate immunity