在抗疟治疗后,自然杀伤细胞有助于实验性疟疾相关急性呼吸窘迫综合征的消退。
NK cells contribute to the resolution of experimental malaria-associated acute respiratory distress syndrome after antimalarial treatment.
作者信息
Pollenus Emilie, Possemiers Hendrik, Knoops Sofie, Prenen Fran, Vandermosten Leen, Pham Thao-Thy, Buysrogge Laura, Matthys Patrick, Van den Steen Philippe E
机构信息
Laboratory of Immunoparasitology, Department of Microbiology, Immunology & Transplantation, Rega Institute for Medical Research, KU Leuven, Leuven, Belgium.
Clinical Immunology Unit, Department of Clinical Sciences, Institute of Tropical Medicine Antwerp, Antwerp, Belgium.
出版信息
Front Immunol. 2024 Sep 17;15:1433904. doi: 10.3389/fimmu.2024.1433904. eCollection 2024.
In both humans and mice, natural killer (NK) cells are important lymphocytes of the innate immune system. They are often considered pro-inflammatory effector cells but may also have a regulatory or pro-resolving function by switching their cytokine profile towards the production of anti-inflammatory cytokines, including interleukin-10 (IL-10) and transforming growth factor-β, and by killing pro-inflammatory immune cells. Here, the role of NK cells in the resolution of malaria lung pathology was studied. Malaria complications, such as malaria-associated acute respiratory distress syndrome (MA-ARDS), are often lethal despite the rapid and efficient killing of parasites with antimalarial drugs. Hence, studying the resolution and healing mechanisms involved in the recovery from these complications could be useful to develop adjunctive treatments. Treatment of -infected C57BL/6 mice with a combination of artesunate and chloroquine starting at the appearance of symptoms was used as a model to study the resolution of MA-ARDS. The role of NK cells was studied using anti-NK1.1 depletion antibodies and NK cell-deficient mice. Using both methods, NK cells were found to be dispensable in the development of MA-ARDS, as shown previously. In contrast, NK cells were crucial in the initiation of resolution upon antimalarial treatment, as survival was significantly decreased in the absence of NK cells. Considerably increased IL-10 expression by NK cells suggested an anti-inflammatory and pro-resolving phenotype. Despite the increase in expression in the NK cells, inhibition of the IL-10/IL-10R axis using anti-IL10R antibodies had no effect on the resolution for MA-ARDS, suggesting that the pro-resolving effect of NK cells cannot solely be attributed to their IL-10 production. In conclusion, NK cells contribute to the resolution of experimental MA-ARDS.
在人类和小鼠中,自然杀伤(NK)细胞都是先天性免疫系统的重要淋巴细胞。它们通常被认为是促炎效应细胞,但也可能具有调节或促消退功能,通过将其细胞因子谱转向产生抗炎细胞因子,包括白细胞介素-10(IL-10)和转化生长因子-β,并通过杀死促炎免疫细胞来实现。在此,研究了NK细胞在疟疾肺部病理消退中的作用。尽管使用抗疟药物能迅速有效地杀死疟原虫,但疟疾并发症,如疟疾相关的急性呼吸窘迫综合征(MA-ARDS),往往是致命的。因此,研究这些并发症恢复过程中的消退和愈合机制可能有助于开发辅助治疗方法。从症状出现开始,用青蒿琥酯和氯喹联合治疗感染疟原虫的C57BL/6小鼠,以此作为研究MA-ARDS消退的模型。使用抗NK1.1耗竭抗体和NK细胞缺陷小鼠来研究NK细胞的作用。如先前所示,使用这两种方法均发现NK细胞在MA-ARDS的发生发展中并非必需。相反,NK细胞在抗疟治疗后启动消退过程中至关重要,因为在没有NK细胞的情况下,存活率显著降低。NK细胞中IL-10表达显著增加,提示其具有抗炎和促消退表型。尽管NK细胞中 表达增加,但使用抗IL10R抗体抑制IL-10/IL-10R轴对MA-ARDS的消退没有影响,这表明NK细胞的促消退作用不能仅仅归因于其IL-10的产生。总之,NK细胞有助于实验性MA-ARDS 的消退。
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