新型宿主途径治理上皮细胞入侵阿斯伯吉勒斯化物
Hong Liu1, Amol C Shetty2, Ashraf S Ibrahim1,3
1Division of Infectious Diseases, Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, California, USA.
Microbiology spectrum
|May 31, 2023
概括
这项研究揭示了新的宿主途径,血小板衍生生长因子BB (PDGF BB) 和孕激素受体 (PGR),在Aspergillus fumigatus感染期间激活. 抑制这些途径减少了真菌入侵,这表明肺上皮细胞对菌感染的反应是常见的.
科学领域:
- 医学微生物学 医学微生物学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 由Aspergillus fumigatus引起的侵入性阿斯伯吉洛症是一种严重的真菌感染,由真菌粘附和肺上皮细胞的入侵引发.
- 了解宿主上皮细胞对A. fumigatus的反应对于开发针对这种致命感染的有效治疗方法至关重要.
研究的目的:
- 研究A549膜上皮细胞对A. fumigatus两种临床分离物 (CEA10和Af293) 感染的转录反应.
- 识别参与肺上皮质对A. fumigatus和其他菌的反应的新型宿主细胞信号通路.
主要方法:
- 转录组测序 (RNA-seq) 用于分析宿主细胞的反应.
- 进行了上游调节器分析,以确定激活的信号通路.
- 药物抑制剂被用于阻断特定途径 (PDGF受体和PGR) 并评估它们对真菌内细胞分裂的影响.
主要成果:
- 两种A. fumigatus菌株在16小时后激活了类似的宿主细胞信号通路,而CEA10菌株在6小时后显示了更早的激活.
- 关键的炎症途径 (TNF,IL-1α,IL-1β,IL-17A,TLR2,TLR4) 被激活,以及血小板衍生的生生长因子BB (PDGF BB) 和孕激素受体 (PGR) 途径.
- 药理上抑制PDGF受体或PGR以添加方式显著抑制了A. fumigatus内细胞形成.
- 预计PDGF BB和PGR通路会被其他菌激活,例如Rhizopus delemar和Rhizopus oryzae.
结论:
- PDGF BB和PGR路径代表了入侵性阿斯伯吉洛症治疗干预的新目标.
- 这些途径可能构成肺上皮细胞对状真菌感染反应的保存机制.
- 针对这些途径可以提供一种共同的治疗策略,用于对抗影响肺部的各种菌感染.
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