Age-dependent cellular reactions of the human immune system of humanized NOD scid gamma mice on LPS stimulus.
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 in vivo, 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: 8-13 wk and 15-22 wk 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-α, 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.
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|2 Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
Anja
A
Rodewohl
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|3 Institute of Clinical Immunology, University of Leipzig, Leipzig, Germany.
Johanna
J
Scholbach
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Anna
A
Leichsenring
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.|2 Translational Centre for Regenerative Medicine, University of Leipzig, Leipzig, Germany.
Margarethe
M
Köberle
1 Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
Franziska
F
Lange
D000328:Adult; D000375:Aging / Q000276:immunology*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D016905:Gram-Negative Bacterial Infections / Q000276:immunology*; D006801:Humans; D007107:Immune System; D007111:Immunity, Cellular; D007223:Infant; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D018805:Sepsis / Q000276:immunology*; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D000099153:Pentraxins
D018952:Antigens, CD34; D002097:C-Reactive Protein; D015850:Interleukin-6; D008070:Lipopolysaccharides; D000683:Serum Amyloid P-Component; D000099153:Pentraxins
Humanized mice; PTX3; sepsis; sepsis mouse model