• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Infection and immunity >Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model
【24h】

Inheritance of Immune Polarization Patterns Is Linked to Resistance versus Susceptibility to Cryptococcus neoformans in a Mouse Model

机译：免疫极化模式的遗传与小鼠模型中新型隐球菌的抗药性和易感性相关

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Genetic background variation between inbred strains accounts for different levels of susceptibility to Cryptococcus neoformans in the mouse infection model. To elucidate the inheritance of immunophenotypic traits and their associations with clearance outcomes during cryptococcal infection, we compared C57BL/6, BALB/c, and their first-generation hybrid, CB6F1 (F1), mice. Mice from each group were infected with C. neoformans (104 CFU) and analyzed at weekly intervals over a 6-week period. BALB/c mice progressively cleared the cryptococcal infection in the lungs and showed a Th1-skewed immune response: a Th1-shifted cytokine profile, modest lung pathology, and no significant elevation in the systemic immunoglobulin E (IgE) level. In contrast, C57BL/6 mice developed a chronic infection with a Th2-skewed immune response: a Th2-shifted cytokine profile, pulmonary eosinophilia, severe lung pathology, elevated serum IgE, fungemia, and cryptococcal dissemination in the central nervous system. F1 mice demonstrated intermediate resistance to C. neoformans, with a stronger resemblance to the immunophenotype of the resistant (BALB/c) mice. F1 mice also demonstrated enhanced pulmonary recruitment of lymphocytes, especially CD8+ T cells, in comparison to both parental strains, suggesting positive heterosis. We conclude that the inheritance of traits responsible for early cytokine induction in the infected lungs and dendritic-cell maturation/activation status in draining nodes is responsible for the intermediate immune response polarization and clearance outcome observed initially in the lungs of F1 mice. The enhanced pulmonary lymphocyte recruitment could be responsible for a gradual shutdown of the undesirable Th2 arm of the immune response and subsequently improved anticryptococcal resistance in F1 mice.
机译：自交系之间的遗传背景差异解释了在小鼠感染模型中对新隐球菌的敏感性水平不同。为了阐明隐球菌感染过程中免疫表型特征的遗传及其与清除结果的关联，我们比较了C57BL / 6，BALB / c和它们的第一代杂种CB6F1（F1）小鼠。每组的小鼠都感染了 C。新甲虫（10 4 CFU）并在6周的时间内每周进行分析。 BALB / c小鼠逐渐清除了肺中的隐球菌感染，并显示了Th1偏向的免疫反应：Th1移位的细胞因子谱，适度的肺部病理学和全身免疫球蛋白E（IgE）水平没有明显升高。相反，C57BL / 6小鼠发生了慢性感染，并伴有Th2偏向的免疫反应：Th2移位的细胞因子，肺嗜酸性粒细胞增多，严重的肺部病理，血清IgE升高，真菌血症和隐球菌在中枢神经系统中的传播。 F1小鼠表现出对C的中等抗性。新甲虫，与耐药（BALB / c）小鼠的免疫表型相似。与两个亲本品系相比，F1小鼠还表现出增强的肺部淋巴细胞募集淋巴细胞，特别是CD8 + T细胞，提示阳性杂种优势。我们得出结论，在感染的肺中负责早期细胞因子诱导的性状的遗传以及在引流淋巴结中树突状细胞成熟/激活状态的遗传是最初在F1小鼠肺中观察到的中间免疫应答极化和清除结果的原因。增强的肺部淋巴细胞募集可能是导致免疫应答不良Th2臂逐渐关闭的原因，并随后改善了F1小鼠的抗隐球菌耐药性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号