Lack of functional selectin-ligand interactions enhances innate immune resistance to systemic Listeria monocytogenes infection.
Lack of functional selectin-ligand interactions enhances innate immune resistance to systemic Listeria monocytogenes infection.
复制标题
功能性选择素-配体相互作用的缺乏增强了对系统性单核细胞增生李斯特菌感染的先天免疫抵抗力。
DOI：
10.1002/jlb.4a1216-499r
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发表时间：
2018
影响因子：
5.5
通讯作者：
Krishnan,Lakshmi
中科院分区：
文献类型：
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作者：
Agbayani,Gerard;Gurnani,Komal;Zafer,Ahmed;Sad,Subash;Krishnan,Lakshmi
选择素-配体相互作用对于白细胞归巢和功能是重要的。选择素-配体相互作用在调节对细胞内感染的免疫中的作用还不完全清楚。缺乏岩藻糖基转移酶-IV和-VII（岩藻糖基转移酶-IV和-VII双敲除，FtDKO）表达的小鼠表现出选择素-配体相互作用的功能缺陷。我们研究了FtDKO小鼠对单核细胞增生李斯特菌（LM）的感染和免疫动力学。相对于野生型（WT）C57 BL/6 J对照，这些小鼠表现出增强的清除感染的能力和增加的对致死剂量的LM感染的存活。这与血液和/或感染器官中的中性粒细胞、单核细胞和树突状细胞（DC）水平升高有关。将骨髓（BM）细胞从FtDKO小鼠连续转移至WT小鼠导致接受者中的中性粒细胞数量增加和LM细菌清除改善。使用抗Ly-6 G（RB 6 - 8 C5）单克隆抗体体内耗竭骨髓先天免疫细胞，特别是嗜中性粒细胞、单核细胞、巨噬细胞和DC，降低了FtDKO小鼠减少LM感染的能力。然而，使用已知专门消耗嗜中性粒细胞的抗Ly-6 G（1A 8）的消耗没有消除FtDKO小鼠对LM感染的增加的抗性，表明其他骨髓先天免疫细胞在该模型中的作用。通过流式细胞术和细胞培养集落形成单位测定对BM造血祖细胞的检查显示，相对于WT小鼠，FtDKO中粒细胞-巨噬细胞祖细胞的频率增加。总体而言，我们的结果表明，尽管白细胞迁移和淋巴细胞归巢缺陷，但功能性选择素配体缺陷增强了先天免疫介导的对系统性LM感染的抗性。
Selectin-ligand interactions are important for leukocyte homing and functionality. The roles of selectin-ligand interactions in modulating immunity to intracellular infections are not completely understood. Mice lacking the expression of fucosyltransferase-IV and -VII (Fucosyltransferase-IV and -VII double knockout, FtDKO) exhibit deficient functionality of selectin-ligand interactions. We addressed the kinetics of infection and immunity toListeria monocytogenes(LM), an intracellular pathogen, in FtDKO mice. These mice exhibited enhanced ability to clear infection and increased survival to a lethal dose of LM infection relative to wild-type (WT) C57BL/6J controls. This was associated with increased levels of neutrophils, monocytes, and dendritic cells (DCs) in the blood and/or infected organs. Adoptive transfer of bone marrow (BM) cells from FtDKO mice to WT mice resulted in enhanced neutrophil numbers and improved clearance of LM bacteria in recipients. In vivo depletion of myeloid innate immune cells, particularly neutrophils, monocytes, macrophages, and DCs, using anti-Ly-6G (RB6-8C5) monoclonal antibody, reduced the ability of FtDKO mice to curtail LM infection. Nevertheless, depletion using anti-Ly-6G (1A8) known to exclusively deplete neutrophils did not abrogate increased resistance of FtDKO mice to LM infection, suggesting a role for other myeloid innate immune cells in this model. Examination of BM hematopoietic progenitors through flow cytometry and cell culture colony-forming unit assay showed increased frequencies of granulocyte-macrophage progenitors in FtDKO relative to WT mice, Overall, our results indicate that functional selectin ligand deficiency enhances innate immune-mediated resistance to systemic LM infection despite defective leukocyte migration and lymphocyte homing.