Fungal Septomics, Leibniz Institute for Natural Product Research and Infection Biology-Hans Knöll Institute, Jena, Germany.
Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
J Infect Dis. 2020 Jun 11;221(12):2060-2071. doi: 10.1093/infdis/jiaa035.
Candida albicans and Candida glabrata are the 2 most prevalent Candida species causing bloodstream infections. Patterns of innate immune activation triggered by the 2 fungi differ considerably.
To analyze human natural killer (NK) cell activation by both species, we performed ex vivo whole-blood infection assays and confrontation assays with primary human NK cells.
C. albicans was a stronger activator for isolated human NK cells than C. glabrata. In contrast, activation of blood NK cells, characterized by an upregulated surface exposure of early activation antigen CD69 and death receptor ligand TRAIL, as well as interferon-γ (IFN-γ) secretion, was more pronounced during C. glabrata infection. NK cell activation in blood is mediated by humoral mediators released by other immune cells and does not depend on direct activation by fungal cells. Cross-talk between Candida-confronted monocyte-derived dendritic cells (moDC) and NK cells resulted in the same NK activation phenotype as NK cells in human blood. Blocking experiments and cytokine substitution identified interleukin-12 as a critical mediator in regulation of primary NK cells by moDC.
Activation of human NK cells in response to Candida in human blood mainly occurs indirectly by mediators released from monocytic cells.
白念珠菌和光滑念珠菌是引起血流感染的两种最常见的念珠菌。这两种真菌引发的固有免疫激活模式有很大的不同。
为了分析这两种真菌对人自然杀伤 (NK) 细胞的激活作用，我们进行了体外全血感染实验和原代人 NK 细胞的对抗实验。
与光滑念珠菌相比，白念珠菌对分离的人 NK 细胞的激活作用更强。相比之下，在光滑念珠菌感染过程中，血液 NK 细胞的激活更为明显，其特征是表面早期激活抗原 CD69 和死亡受体配体 TRAIL 的表达上调，以及干扰素-γ (IFN-γ) 的分泌。血液中 NK 细胞的激活是由其他免疫细胞释放的体液介质介导的，而不依赖于真菌细胞的直接激活。与念珠菌对抗的单核细胞衍生的树突状细胞 (moDC) 和 NK 细胞之间的串扰导致与血液中 NK 细胞相同的 NK 激活表型。阻断实验和细胞因子替代鉴定出白细胞介素-12 是 moDC 调节原代 NK 细胞的关键介质。
人血液中对念珠菌的 NK 细胞激活主要是通过单核细胞释放的介质间接发生的。
