Cryptococcus inositol utilization modulates the host protective immune response during brain infection.
Cryptococcus inositol utilization modulates the host protective immune response during brain infection.
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隐球菌肌醇利用调节脑感染期间宿主保护性免疫反应
DOI：
10.1186/s12964-014-0051-0
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发表时间：
2014-09-10
期刊：
影响因子：
--
通讯作者：
Xue C
中科院分区：
文献类型：
--
作者：
Liu TB;Subbian S;Pan W;Eugenin E;Xie J;Xue C
背景：新型隐球菌是HIV/AIDS患者中真菌性脑膜炎最常见的病因，如果不进行适当的治疗，这种疾病是致命的。导致隐球菌性脑膜脑炎的脑部疾病发展的潜在机制仍不完全清楚。我们以前已经证明，肌醇转运蛋白（ITR）所需的隐球菌的毒力。C. itr 1a Δ itr 3c Δ双突变体neoformans在小鼠脑内感染模型中的毒力减弱;表明Itr 1a和Itr 3c是脑感染期间完全毒力所需的，尽管在感染的brain.Results中突变株和野生型菌株之间的生长速率相似：为了了解与itr 1a Δ itr 3c Δ双突变株感染相关的免疫病理学，我们研究了小鼠脑感染期间宿主免疫应答的分子相关性。我们使用全基因组转录组鸟枪测序（RNA-Seq）和定量实时PCR（qRT-PCR）方法来检查感染大脑中的宿主基因表达谱。我们的研究结果表明，与野生型相比，突变体感染小鼠大脑导致与宿主保护性免疫相关的细胞网络/途径的显着激活。大多数显著差异表达的基因（SDEG）是免疫细胞网络的一部分，如肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）调节子，表明与野生型相比，突变体感染会产生更强的宿主免疫应答。有趣的是，葡萄糖醛酸甘露聚糖（GXM）的分泌显着减少，观察itr 1a Δ itr 3c Δ突变体细胞，表明肌醇利用途径在胶囊production.Conclusions中发挥作用：由于胶囊已被证明会影响宿主反应期间隐球菌-宿主相互作用，我们的研究结果表明，减少GXM生产可能有助于增加免疫激活的mucococcus感染的动物。
Background:Cryptococcus neoformans is the most common cause of fungal meningitis among individuals with HIV/AIDS, which is uniformly fatal without proper treatment. The underlying mechanism of disease development in the brain that leads to cryptococcal meningoencephalitis remains incompletely understood. We have previously demonstrated that inositol transporters (ITR) are required for Cryptococcus virulence. The itr1aΔ itr3cΔ double mutant of C. neoformans was attenuated for virulence in a murine model of intra-cerebral infection; demonstrating that Itr1a and Itr3c are required for full virulence during brain infection, despite a similar growth rate between the mutant and wild type strains in the infected brain.Results:To understand the immune pathology associated with infection by the itr1aΔ itr3cΔ double mutant, we investigated the molecular correlates of host immune response during mouse brain infection. We used genome-wide transcriptome shotgun sequencing (RNA-Seq) and quantitative real-time PCR (qRT-PCR) methods to examine the host gene expression profile in the infected brain. Our results show that compared to the wild type, infection of mouse brains by the mutant leads to significant activation of cellular networks/pathways associated with host protective immunity. Most of the significantly differentially expressed genes (SDEG) are part of immune cell networks such as tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) regulon, indicating that infection by the mutant mounts a stronger host immune response compared to the wild type. Interestingly, a significant reduction in glucuronoxylomannan (GXM) secretion was observed in the itr1aΔ itr3cΔ mutant cells, indicating that inositol utilization pathways play a role in capsule production.Conclusions:Since capsule has been shown to impact the host response during Cryptococcus-host interactions, our results suggest that the reduced GXM production may contribute to the increased immune activation in the mutant-infected animals.
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影响因子：
5.2
作者：
Liu TB;Perlin DS;Xue C
通讯作者：
Xue C
影响因子：
3.1
作者：
Lee, Anthony;Toffaletti, Dena L.;Perfect, John R.
通讯作者：
Perfect, John R.
影响因子：
3.1
作者：
Cox, GM;Mukherjee, J;Perfect, JR
通讯作者：
Perfect, JR
DOI：
10.1084/jem.173.3.755
发表时间：
1991-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hill JO;Harmsen AG
通讯作者：
Harmsen AG
影响因子：
3.4
作者：
Jong, Ambrose;Wu, Chun-Hua;Huang, Sheng-He
通讯作者：
Huang, Sheng-He