Age-dependent cellular reactions of the human immune system of humanized NOD scid gamma mice on LPS stimulus

作者：Rodewohl Anja; Scholbach Johanna; Leichsenring Anna; Koeberle Margarethe; Lange Franziska^*

来源：Innate Immunity, 2017, 23(3): 258-275.

DOI：10.1177/1753425917690814

• Humanized mice
• PTX3
• sepsis
• sepsis mouse model

Despite sepsis being a life-threatening disease, targeted drugs that improve the therapy of affected patients are still lacking. Infants and adults differ in the maturity level of their immune system and this results in distinct reactions to Gram-negative bacteria. To study reactions of human immune cells invivo, we used NOD scid gamma mice transplanted with human CD34(+) stem cells to engraft a functional human immune system. Human cells undergo differentiation and maturation in these mice after transplantation and, accordingly, animals were divided into two groups: 8-13wk and 15-22wk after transplantation. Endotoxemia was induced by injecting LPS. Six h later, mice were euthanized. In both groups, LPS stimulation induced a decrease of CD14(+) monocytes in peripheral blood, an up-regulation of activation markers on different cell subsets such as myeloid dendritic cells, and a release of the human cytokines TNF-, IL-6 and IL-10. However, significant differences were detected with regard to the amounts of released cytokines, and 8-13-wk-old mice produced more IL-6, while PTX3 was mainly released by 15-22-wk-old animals. Thus, here we provide a potential model for preclinical research of sepsis in infants and adults.

• 出版日期2017-4