Immunology Laboratory, Department of Zoology, University of Calcutta. 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
Immunology Laboratory, Department of Zoology, University of Calcutta. 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
Cytokine. 2022 Jul;155:155910. doi: 10.1016/j.cyto.2022.155910. Epub 2022 May 18.
Myeloid derived suppressor cells (MDSCs) are a group of heterogeneous cell populations that can suppress T cell responses. Various aspects of MDSCs in regulating immune responses in several cancer and infectious diseases have been reported till date. But the role and regulation of MDSCs have not been systematically studied in the context of malaria. This study depicts the phenotypic and functional characteristics of splenic MDSCs and how they regulate Th-17 mediated immune response during Experimental Cerebral Malaria (ECM). Flow cytometric analysis reveals that MDSCs in the spleen and bone marrow expand at 8 dpi during ECM. Among subtypes of MDSCs, PMN-MDSCs show significant expansion in the spleen but M-MDSCs remain unaltered. Functional analysis of sorted MDSCs from spleens of Plasmodium berghei ANKA (PbA) infected mice shows suppressive nature of these cells and high production of Nitric oxide (NO). Besides, MDSCs were also found to express various inflammatory markers during ECM suggesting the M1 type phenotype of these cells. In-vivo depletion of MDSCs by the use of Anti Gr-1 increases mice survival but doesn't significantly alter the parasitemia. Previously, it has been reported that Treg/Th-17 balance in the spleen is skewed towards Th-17 during ECM. Depletion of MDSCs was found to regulate Th-17 percentages to homeostatic levels and subvert various inflammatory changes in the spleen. Among different factors, IL-6 was found to play an important role in the expansion of MDSCs and expression of inflammatory markers on MDSCs in a STAT3-dependent manner. These findings provide a unique insight into the role of IL-6 in the expansion of the MDSC population which causes inflammatory changes and increased Th-17 responses during ECM.
髓系来源的抑制细胞（MDSCs）是一群异质性细胞群体，能够抑制 T 细胞反应。迄今为止，已有报道称 MDSCs 在几种癌症和感染性疾病中调节免疫反应的各个方面。但是，在疟疾的背景下，MDSCs 的作用和调节尚未得到系统研究。本研究描述了脾 MDSCs 的表型和功能特征，以及它们在实验性脑疟疾（ECM）中如何调节 Th-17 介导的免疫反应。流式细胞术分析显示，在 ECM 期间，脾脏和骨髓中的 MDSCs 在 8dpi 时扩增。在 MDSC 的亚型中，PMN-MDSCs 在脾脏中显著扩增，而 M-MDSCs 保持不变。从感染疟原虫伯氏疟原虫 ANKA（PbA）的小鼠脾脏中分选的 MDSCs 的功能分析表明这些细胞具有抑制作用，并产生大量一氧化氮（NO）。此外，在 ECM 过程中还发现 MDSCs 表达各种炎症标志物，表明这些细胞具有 M1 表型。通过使用抗 Gr-1 体内耗竭 MDSCs 可增加小鼠的存活率，但不会显著改变寄生虫血症。先前有报道称，在 ECM 期间，脾脏中的 Treg/Th-17 平衡偏向 Th-17。耗竭 MDSCs 可调节 Th-17 百分比至生理水平，并颠覆脾脏中的各种炎症变化。在不同的因素中，IL-6 被发现以 STAT3 依赖的方式在 MDSC 的扩增和 MDSC 上炎症标志物的表达中起重要作用。这些发现为 IL-6 在 MDSC 群体扩张中的作用提供了独特的见解，该群体在 ECM 期间导致炎症变化和增加的 Th-17 反应。
