Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2
Authors: Yong Fu, Yan Ding, Qinghui Wang, Feng Zhu, Yulong Tan, Xiao Lu, Bo Guo, Qingfeng Zhang, Yaming Cao, Taiping Liu, Liwang Cui, and Wenyue Xu
Malaria parasites suppress host immune responses to facilitate their survival, but the underlying mechanism remains elusive. Here, we found that blood-stage malaria parasites predominantly induced CD4+Foxp3+CD25+ regulatory T cells to release soluble fibrinogen-like protein 2 (sFGL2), which substantially enhanced the infection. This was attributed to the capacity of sFGL2 to inhibit macrophages from releasing monocyte chemoattractant protein-1 (MCP-1) and to sequentially reduce the recruitment of natural killer/natural killer T cells to the spleen and the production of interferon-γ. sFGL2 inhibited c-Jun N-terminal kinase phosphorylation in the Toll-like receptor 2 signaling pathway of macrophages dependent on FcγRIIB receptor to release MCP-1. Notably, sFGL2 were markedly elevated in the sera of patients with malaria, and recombinant FGL2 substantially suppressed Plasmodium falciparum from inducing macrophages to release MCP-1. Therefore, we highlight a previously unrecognized immune suppression strategy of malaria parasites and uncover the fundamental mechanism of sFGL2 to suppress host innate immune responses.
Reference: YONG FU, YAN DING, QINGHUI WANG, FENG ZHU, YULONG TAN, XIAO LU, BO GUO, QINGFENG ZHANG, YAMING CAO, TAIPING LIU, LIWANG CUI, WENYUE XU. SCIENCE ADVANCES FEB 2020: EAAY9269. Retrieved from https://advances.sciencemag.org/
The authors used Bio X Cell's anti-mouse IFNγ (Clone: XMG1.2), anti-mouse/human/rat CCL2 (MCP-1) (Clone: 2H5), anti-mouse NK1.1 (Clone: PK136), and anti-mouse CD25 (IL-2Rα)(Clone: PC-61.5.3) in this research study.