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临床分离的Cryptococcus neoformans的高病毒性Type-1/Type-17表型是特定于A/J小鼠的

Minna Ding¹, Katrina M Jackson^1,2, Madeline Harris-Gordon¹

¹Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA.

Infection and immunity

|March 3, 2025

概括

主体免疫反应和小鼠遗传学决定了Cryptococcus neoformans的毒性. 在A/J小鼠中,一种高病毒性表型涉及免疫细胞招募的增加和特定的细胞因子概况,而在C57BL/6J小鼠中没有观察到这种情况.

科学领域:

* 免疫学免疫学
* 传染病传染病
* 微生物学微生物学

背景情况:

*新型菌 (Cryptococcus neoformans) 引起菌脑膜炎,特别是在免疫力低下的人群中.
*宿主和病原体因素影响疾病的结果,在C. neoformans中已知具有特定菌株的毒性差异.
*宿主免疫学和遗传背景对C. neoformans感染结果的影响尚不清楚.

研究的目的:

* 调查同系老鼠菌株的免疫学和遗传背景如何影响C. neoformans感染期间的疾病结果.
* 确定特定C. neoformans分离物的高病毒性表型是否取决于宿主免疫反应和小鼠遗传背景.

主要方法:

* A/J和C57BL/6J小鼠的鼻腔感染高病毒性C.neoformans分离物 (UgCl247,UgCl422,UgCl236) 和参考菌株 (KN99α).
* 分析感染小鼠免疫细胞招募 (中性粒细胞,T细胞) 和细胞因子 (IFNγ,IL-17) 的分析.
*评估肺 CD4 T 细胞中的 Th1 (CXCR3,Tbet) 和 Th17 (RORγT) 标记表达.
*在A/J小鼠背景中评估已知的遗传突变.

主要成果:

*与KN99α感染相比,感染过病毒性分离物的A/J小鼠显示中性粒细胞和T细胞招募增加,IFNγ和IL-17水平升高,Th1/Th17标志物增强.
*C57BL/6J小鼠感染了相同的分离物没有表现出高病毒性表型;病毒性与KN99α对照相似.
*C57BL/6J小鼠的免疫反应在所有测试的隔离物中都是相似的.
*A/J小鼠的高病毒性表型不能归因于已知的遗传突变.

结论:

* 某些C. neoformans分离物的高病毒性表型取决于宿主免疫反应和遗传背景.
* A/J小鼠具有独特的免疫反应,其特点是炎症增加和针对高病毒性分离物的特定T细胞概况.
*C57BL/6J小鼠表现出不那么明显和统一的反应,掩盖了这些隔离物的高毒性.
* 一种同系小鼠吸入模型是有效的解剖宿主和致病原体特异性因素影响C. neoformans疾病进展.

关键词:

这是Cryptococcus neoformans的新型菌.第1类免疫反应第17类免疫反应这种疾病叫做cryptococcosis.损害应对框架的框架主体-病原体相互作用过度病毒性过度病毒性免疫复原炎症综合征免疫复原炎症综合征

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