- 作者: Zivan M. Babic, Filip Z. Zunic, Jelena M. Pantic, Gordana D. Radosavljevic, Ivan P. Jovanovic, Nebojsa N. Arsenijevic and Miodrag L. Lukic
- 作者服務機構: 1.Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia 2. Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, Kragujevac 34000, Serbia
- 中文摘要:
- 英文摘要:
Background
Sepsis is a life-threatening disease mediated by profound disturbances in systemic inflammatory response to infection. IL-33 is multifunctional regulator of numerous aspects of innate and adaptive immune response. The aim of this article was to further evaluate the role of IL-33 receptor (ST2) in different pathways of innate immunity during early polymicrobial sepsis.
Methods
Polymicrobial sepsis was induced using cecal ligation and puncture (CLP) model in ST2 deficient (ST2−/−) and wild type BALB/c mice. Peritoneal and spleen cells were isolated for further phenotyping. Apoptosis was determined by immunohistochemistry and flow cytometry.
Results
Deletion of ST2 leads to increased susceptibility to early manifestations of sepsis as evaluated by clinical signs and survival. These are accompanied by decrease in the total number of neutrophils, eosinophils and mast cells in peritoneal cavity 12 h after CLP. In early sepsis there was also low number of precursors of myeloid cells in particular CD11b+Ly6G+Ly6Clow cells in spleen of ST2−/− mice. Although the number of NK cells in the spleen was similar, there were significant differences in the presence of inflammatory IFN-γ and IL-17 producing NK cells. Further, ST2 deletion affects the phenotype and maturation of dendritic cell in sepsis. The total number of dendritic cells in the spleen was lower as well as IL-12 expressing dendritic cells. Finally, there was higher frequency of active caspase-3 positive and early apoptotic cells, in particular CD11c positive cells, in spleen of septic ST2−/− mice.
Conclusion
Taken together, our data provide the evidence that ST2 deficiency in early phase of sepsis downregulates myeloid precursors, inflammatory NK and dendritic cells. - 中文關鍵字:
- 英文關鍵字: ST2, IL-33, Sepsis, Myeloid precursors, NK cells, Dendritic cells