期刊
CYTOKINE
卷 155, 期 -, 页码 -出版社
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.cyto.2022.155910
关键词
Malaria; Plasmodium berghei ANKA; Myeloid derived suppressor cells; Th-17; IL-6; Inflammation
资金
- Department of Science and Technology [INT/RUS/RFBR/P-331, 5/13/23/2019/NCD-III, 27 (0323) /17/EMR-II]
- Department of Science and Technology, Govt. of India [INT/RUS/RFBR/P-331]
- Indian Council of Medical research [5/13/23/2019/NCD-III]
- Council of Scientific and Industrial Research [27 (0323) /17/EMR-II]
- CSIR , India
- University Grants Commission (UGC) , India
This study investigates the role and regulation of MDSCs in the context of malaria. The results show that MDSCs expand in the spleen and bone marrow during Experimental Cerebral Malaria (ECM) and exhibit suppressive properties and high production of Nitric oxide (NO). Depletion of MDSCs regulates immune balance and inflammatory changes. IL-6 plays an important role in the expansion of MDSCs and expression of inflammatory markers.
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.
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