Mukherjee Saikat, Ghosh Pronabesh, Ghosh Soubhik, Sengupta Anirban, Sarkar Samrat, Chatterjee Rimbik, Saha Atreyee, Bawali Sriparna, Choudhury Abhishek, Daptary Altamas Hossain, Gangopadhyay Anwesha, Keswani Tarun, Bhattacharyya Arindam
Immunology Laboratory, Department of Zoology, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019, West Bengal, India.
Centre for Infectious Medicine, Department of Medicine Huddinge, Karolinksa Institutet, 14152 Stockholm, Sweden.
Pathogens. 2024 Oct 8;13(10):877. doi: 10.3390/pathogens13100877.
The onset of malaria causes the induction of various inflammatory markers in the host's body, which in turn affect the body's homeostasis and create several cerebral complications. Polarization of myeloid-derived suppressor cells (MDSCs) from the classically activated M1 to alternatively activated M2 phenotype increases the secretion of pro-inflammatory molecules. Treatment with recombinant IL-33 (rIL-33) not only alters this MDSC's polarization but also targets the glycolysis pathway of the metabolism in MDSCs, rendering them less immunosuppressive. Along with that, the Helper T-cells subset 17 (Th17)/T regulatory cells (Tregs) ratio is skewed towards Th17, which increases inflammation by producing more IL-17. However, treating with rIL-33 also helps to restore this ratio, which brings back homeostasis. During malaria infection, there is an upregulation of IL-12 production from dendritic cells along with a distorted myeloid dendritic cells (mDC)/plasmacytoid dendritic cells (pDC) ratio towards mDCs promoting inflammation. Administering rIL-33 will also subvert this IL-12 production and increase the population of pDC in the host's immune system during malaria infection, thus restoring mDC/pDC to homeostasis. Therefore, treatment with rIL-33 to reduce the pro-inflammatory signatures and maintenance of immune homeostasis along with the increase in survivability could be a potential therapeutic approach for cerebral malaria.
疟疾的发作会导致宿主体内多种炎症标志物的产生，进而影响身体的稳态并引发多种脑部并发症。髓源性抑制细胞（MDSCs）从经典激活的M1表型向交替激活的M2表型极化会增加促炎分子的分泌。重组白细胞介素-33（rIL-33）治疗不仅会改变这种MDSC的极化，还会靶向MDSCs代谢中的糖酵解途径，使其免疫抑制作用减弱。与此同时，辅助性T细胞17（Th17）/调节性T细胞（Tregs）的比例向Th17倾斜，通过产生更多的白细胞介素-17来加剧炎症。然而，用rIL-33治疗也有助于恢复这一比例，从而恢复体内平衡。在疟疾感染期间，树突状细胞产生白细胞介素-12的量上调，同时髓样树突状细胞（mDC）/浆细胞样树突状细胞（pDC）的比例向促进炎症的mDCs倾斜。给予rIL-33还会抑制这种白细胞介素-12的产生，并在疟疾感染期间增加宿主免疫系统中pDC的数量，从而使mDC/pDC恢复到体内平衡。因此，用rIL-33治疗以减少促炎特征、维持免疫稳态并提高生存率可能是治疗脑型疟疾的一种潜在治疗方法。
