Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice.
Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice.
复制标题
DOI：
10.1242/bio.029785
复制
发表时间：
2018-02-13
期刊：
影响因子：
2.4
通讯作者：
Poluektova LY
中科院分区：
文献类型：
--
作者：
Dagur RS;Wang W;Cheng Y;Makarov E;Ganesan M;Suemizu H;Gebhart CL;Gorantla S;Osna N;Poluektova LY
人类免疫缺陷病毒1型（HIV-1）感染损害肝功能，肝脏疾病已成为感染患者发病的主要原因。HIV-1引起的肝损伤的免疫病理尚不清楚。我们使用人类免疫系统和肝细胞双重重组的嵌合小鼠来解决该模型与全身性感染下人类肝细胞存活相关的病理生物学问题的相关性。TK-NOG雄性小鼠移植不匹配的人造血干细胞/祖细胞和肝细胞，监测血液中人白蛋白浓度和人免疫细胞的存在，检测肝细胞和免疫重建，小鼠感染HIV-1。与未感染的小鼠相比，感染hiv -1的动物表现出人白蛋白浓度下降，人肝细胞百分比显著减少。人白蛋白水平的下降与肝脏中CD4+细胞的下降和HIV-1病毒载量的增加相关。通过上调il - 23、CXCL10和多种toll样受体的表达，与未感染的动物相比，HIV-1感染在hiv感染小鼠的肝脏免疫环境中引发了促炎反应。体内与HIV-1感染相关的炎症反应可能导致肝细胞耗竭和功能障碍。双重重构TK-NOG小鼠模型是研究HIV-1肝细胞相关免疫发病机制的可行平台。摘要：我们描述了一个模型，该模型概括了人类HIV-1感染引起的肝损伤的多个组成部分，包括肝脏CD4+细胞减少、白蛋白水平降低、肝脏免疫激活和人类肝细胞存活。
Human immunodeficiency virus type 1 (HIV-1) infection impairs liver function, and liver diseases have become a leading cause of morbidity in infected patients. The immunopathology of liver damage caused by HIV-1 remains unclear. We used chimeric mice dually reconstituted with a human immune system and hepatocytes to address the relevance of the model to pathobiology questions related to human hepatocyte survival in the presence of systemic infection. TK-NOG males were transplanted with mismatched human hematopoietic stem/progenitor cells and hepatocytes, human albumin concentration and the presence of human immune cells in blood were monitored for hepatocytes and immune reconstitution, and mice were infected with HIV-1. HIV-1-infected animals showed a decline in human albumin concentration with a significant reduction in percentage of human hepatocytes compared to uninfected mice. The decrease in human albumin levels correlated with a decline in CD4+ cells in the liver and with an increase in HIV-1 viral load. HIV-1 infection elicited proinflammatory response in the immunological milieu of the liver in HIV-infected mice compared to uninfected animals, as determined by upregulation of IL23, CXCL10 and multiple toll-like receptor expression. The inflammatory reaction associated with HIV-1 infection in vivo could contribute to the depletion and dysfunction of hepatocytes. The dual reconstituted TK-NOG mouse model is a feasible platform to investigate hepatocyte-related HIV-1 immunopathogenesis. Summary: We describe a model that recapitulates multiple components of liver damage by HIV-1 infection as in humans, including reduced liver CD4+ cells, albumin levels, liver immune activation and human hepatocyte survival.
登录
查看更多内容
DOI：
10.1016/j.jcmgh.2017.10.004
发表时间：
2018
影响因子：
7.2
作者：
Ganesan M;Tikhanovich I;Vangimalla SS;Dagur RS;Wang W;Poluektova LI;Sun Y;Mercer DF;Tuma D;Weinman SA;Kharbanda KK;Osna NA
通讯作者：
Osna NA
DOI：
10.1097/qad.0b013e328357f5ad
发表时间：
2012-11-13
期刊：
AIDS (London, England)
影响因子：
--
作者：
Dash PK;Gendelman HE;Roy U;Balkundi S;Alnouti Y;Mosley RL;Gelbard HA;McMillan J;Gorantla S;Poluektova LY
通讯作者：
Poluektova LY
影响因子：
1.5
作者：
Graham, Susan M.;Baeten, Jared M.;McClelland, R. Scott
通讯作者：
McClelland, R. Scott
影响因子：
4.6
作者：
Araínga M;Su H;Poluektova LY;Gorantla S;Gendelman HE
通讯作者：
Gendelman HE
影响因子：
4.8
作者：
Kong L;Cardona Maya W;Moreno-Fernandez ME;Ma G;Shata MT;Sherman KE;Chougnet C;Blackard JT
通讯作者：
Blackard JT