对Cryptococcus neoformans的敏感性 感染布鲁顿的氨酸激酶抑制的感染
Julia A Messina1, Charles D Giamberardino1, Jennifer L Tenor1
1Duke University School of Medicine, Department of Medicine, Division of Infectious Diseases, Durham, North Carolina, USA.
Infection and immunity
|July 5, 2023
概括
布鲁顿的氨酸激酶 (BTK) 抑制在小鼠模型中没有改变Cryptococcus neoformans感染的严重程度. 需要进一步的研究来了解BTK抑制剂在真菌感染易感性中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 药理学 药理学是指药理学的学科.
背景情况:
- 接受布鲁顿氨酸激酶 (BTK) 抑制剂 (如易布鲁替尼) 的患者表现出增加的真菌感染风险.
- 关联BTK抑制与对真菌感染易感性增加的确切机制尚不清楚.
研究的目的:
- 为了调查Cryptococcus neoformans感染的严重程度是否取决于当布鲁顿氨酸激酶 (BTK) 被抑制时的特定隔离物.
- 为了确定阻断BTK是否会影响在临床前小鼠模型中真菌感染的严重程度.
主要方法:
- 四个临床Cryptococcus neoformans分离物与BTK淘汰 (KO) 和野生型 (WT) 小鼠中的参考菌株 (H99,A1-35-8) 的比较.
- 感染是通过鼻内,口吸入和静脉输入途径诱导的,严重程度根据生存率和真菌负担进行评估.
- 小鼠每天接受IBRUTINIB (25 mg/kg) 或载体的腹腔内注射.
主要成果:
- 在BTK KO模型中,在不同感染路径中没有观察到对真菌负担的孤立依赖作用.
- 与野生类型对照相比,BTK淘汰和易布鲁替尼治疗都没有显著改变感染严重程度.
- 在四个临床分离物中,两种与H99参考菌株相比呈现出降低的毒性,显示出更长的存活时间和更少的脑部感染.
结论:
- 在BTK淘汰赛小鼠模型中,Cryptococcus neoformans感染的严重程度并不依赖于隔离物.
- 在这个模型中,BTK淘汰和ibrutinib治疗没有显著改变感染严重程度.
- 需要进行进一步的研究,以完善小鼠模型,准确地反映在接受BTK抑制剂治疗的患者中观察到的对真菌感染的敏感性增加.
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