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髓单核细胞和CD8 T细胞的不同行为是肝脏对……反应的基础。 (原文中“to”后面缺少具体内容)

Distinct behavior of myelomonocytic cells and CD8 T cells underlies the hepatic response to .

作者信息

Velázquez Peter, Williams Cassandra, Leiner Ingrid, Pamer Eric G, Dustin Michael L

机构信息

Molecular Pathogenesis Program, The Helen L. and Martin S. Kimmel Center for Biology and Medicine, Skirball Institute of Biomolecular Medicine, New York, NY, 10016, USA.

Department of Microbiology and Immunology, Indiana University School of Medicine - South Bend, South Bend, IN, 46617, USA.

出版信息

Wellcome Open Res. 2018 Apr 24;3:48. doi: 10.12688/wellcomeopenres.12941.1. eCollection 2018.

Abstract

: The immune response to (LM) is characterized by formation of leukocyte rich foci of infection in liver and spleen.  Although much has been gained in our understanding of immune response through the study of LM, little is known about spatio-temporal regulation of immune response to Listeria in liver. We utilize a combination of molecular, genetic and intravital microscopic approaches to gain insight into the dynamics of foci and leukocyte behavior during hepatic Listeriosis.  : LM foci efficiently exclude blood flow, indicating the presence of a barrier separating the foci and healthy tissue.  Despite this barrier, sinusoidal myelomonocytic cells readily enter or transiently interact with cells at the edge of foci of infection.  Next, utilizing L9.6 transgenic CD8 T cells specific for an endogenously processed LM antigen, p60 217-225, along with LM deficient in this epitope, we define the role of TCR in T cell migratory behavior in infected liver.  Surprisingly, T cell behavior varies with micro-anatomic locale.  Near foci, non-specific adhesion mechanisms dominate lymphocyte behavior.  Antigen specific effects on motility became detectable only distal to foci.  These data suggest that LM antigens act in a paracrine manner to mediate protection from Listeriosis in the liver.

摘要

对单核细胞增生李斯特菌(LM)的免疫反应特征是在肝脏和脾脏中形成富含白细胞的感染灶。尽管通过对LM的研究,我们在理解免疫反应方面取得了很大进展,但对于肝脏中对李斯特菌免疫反应的时空调节知之甚少。我们利用分子、遗传和活体显微镜方法相结合,来深入了解肝李斯特菌病期间感染灶的动态变化和白细胞行为。LM感染灶能有效阻止血流,表明存在将感染灶与健康组织分隔开的屏障。尽管有这道屏障,肝血窦中的骨髓单核细胞仍能轻易进入感染灶边缘或与那里的细胞短暂相互作用。接下来,我们利用针对内源性加工的LM抗原p60 217 - 225的L9.6转基因CD8 T细胞,以及缺乏该表位的LM,来确定T细胞受体(TCR)在感染肝脏中T细胞迁移行为中的作用。令人惊讶的是,T细胞行为因微解剖位置而异。在感染灶附近,非特异性黏附机制主导淋巴细胞行为。对抗原特异性的运动影响仅在感染灶远端才可检测到。这些数据表明,LM抗原以旁分泌方式发挥作用,介导对肝脏李斯特菌病的保护。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eac6/5958313/15e498172834/wellcomeopenres-3-14032-g0000.jpg

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