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Platelets Modulate IFN-γ Production against Candida albicans in Peripheral Blood Mononuclear Cells via Prostaglandins
The Journal of Immunology ( IF 4.4 ) Pub Date : 2019-11-25 , DOI: 10.4049/jimmunol.1900599
Intan M W Dewi 1, 2, 3 , Floor E Aleva 4, 5 , Vesla I Kullaya 4, 6 , Fadel M Garishah 2, 4 , Quirijn de Mast 2, 4 , André J A M van der Ven 2, 4 , Frank L van de Veerdonk 2, 4
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Key Points Platelets modulate IFN-γ production by PBMCs in response to C. albicans. The effect required direct contact between platelets and monocytes. Platelet modulation of the Th1 response was dependent on PGE2. Platelets are known to have immunomodulatory properties. They modulate immune responses of leukocytes against various pathogens, including fungi. Candida albicans can cause systemic infection in immunocompromised individuals that is associated with a high mortality and morbidity. In the current study, we explored the role of platelets in antifungal host defense against C. albicans. PBMCs were stimulated with heat-killed (HK) C. albicans in the presence or absence of isolated washed platelets. Cytokines were quantified from culture supernatants by ELISA. Inhibition of platelet receptors and cytokine pathways were used to elucidate the mechanisms involved in platelet–leukocyte interaction. In the presence of platelets, PBMCs produced less IFN-γ upon stimulation with HK C. albicans. This effect was dependent on the direct contact between platelets and leukocytes but was independent of the platelet GPIb and P-selectin receptors. The attenuation of IFN-γ was not a direct effect on T cells but was dependent on the presence of APC and T cells. Platelets did not modulate the Th-1–polarizing cytokines IL-12 and IL-18. The addition of PG (PGE2) further diminished IFN-γ levels in PBMCs, and supplementation of cells with nonsteroidal anti-inflammatory drugs was able to restore the level of IFN-γ. Overall, we show that modulation of the Th1 response against C. albicans by platelets is dependent on PGs.

中文翻译:

血小板通过前列腺素调节外周血单核细胞中针对白色念珠菌的 IFN-γ 产生

关键点 血小板调节 PBMC 产生的 IFN-γ 以响应白色念珠菌。该效应需要血小板和单核细胞之间的直接接触。Th1 反应的血小板调节依赖于 PGE2。已知血小板具有免疫调节特性。它们调节白细胞对各种病原体(包括真菌)的免疫反应。白色念珠菌可在免疫功能低下的个体中引起全身感染,这与高死亡率和发病率有关。在当前的研究中,我们探讨了血小板在抗真菌宿主防御白色念珠菌中的作用。在存在或不存在分离的洗涤血小板的情况下,用热灭活 (HK) 白色念珠菌刺激 PBMC。通过ELISA从培养物上清液中定量细胞因子。血小板受体和细胞因子通路的抑制被用来阐明血小板-白细胞相互作用的机制。在血小板存在的情况下,PBMC 在用 HK C. albicans 刺激后产生较少的 IFN-γ。这种作用依赖于血小板和白细胞之间的直接接触,但不依赖于血小板 GPIb 和 P-选择素受体。IFN-γ 的减弱不是对 T 细胞的直接影响,而是取决于 APC 和 T 细胞的存在。血小板不调节 Th-1 极化细胞因子 IL-12 和 IL-18。PG (PGE2) 的添加进一步降低了 PBMC 中的 IFN-γ 水平,并且用非甾体抗炎药补充细胞能够恢复 IFN-γ 的水平。总的来说,我们表明血小板对白色念珠菌的 Th1 反应的调节依赖于 PG。
更新日期:2019-11-25
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