在抗逆转录病毒治疗的HIV感染中,持续的肺炎球菌定居与鼻腔炎症有关
Joseph Aston Phiri1,2, Lusako Lucky Sibale3,4, Gloria Kapira3,4
1Malawi-Liverpool-Wellcome Research Programme, Blantyre, Malawi. jphiri@mlw.mw.
长期的抗逆转录病毒疗法 (ART) 在艾滋病毒感染者 (PLHIV) 中无法恢复鼻腔免疫力. 持续的炎症和免疫细胞功能障碍有助于肺炎球菌的携带,这表明新的治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 传染性疾病 传染性疾病
- 艾滋病毒研究 艾滋病毒研究
背景情况:
- 接受抗逆转录病毒疗法 (ART) 的艾滋病毒感染者 (PLHIV) 经历了对肺炎球菌感染的敏感性增加.
- 通过ART进行系统性病毒抑制并不能完全恢复呼吸道中的粘膜免疫力.
研究的目的:
- 调查长期ART对PLHIV的鼻膜免疫的持续影响.
- 为了确定与增加的肺炎球菌殖民感相关的免疫特征,在ART上的PLHIV中.
主要方法:
- 使用流式细胞计和单细胞转录学来分析鼻腔免疫细胞.
- 进行了中性粒细胞功能测试,以评估氧化爆发能力.
- 基因表达分析确定了上皮细胞和T细胞概况以及与衰老相关的分泌表现型 (SASP).
主要成果:
- 长期的ART (超过1年) 并没有恢复PLHIV的鼻腔粘膜免疫力.
- 观察到一种持久的免疫特征,其特征是表皮驱动的中性恋炎症,T细胞疲劳和细胞衰老.
- 中性粒细胞表现出线粒体压力,SASP基因表达和功能受损,特别是在肺炎球菌携带者中.
- 皮质细胞上调调节了中性粒细胞招募配体,鼻腔T细胞表现出亲细胞亡和疲劳的特征.
- 中性炎症与肺炎球菌载体密度相关,这表明反循环.
结论:
- 组织特异性免疫失调在PLHIV中持续存在,尽管有ART.
- 向表皮-免疫信号或中性粒细胞衰老可能提供新的策略,以减少PLHIV的呼吸道病原体负担.
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