PT  - JOURNAL ARTICLE
AU  - Fu, Yong
AU  - Ding, Yan
AU  - Wang, Qinghui
AU  - Zhu, Feng
AU  - Tan, Yulong
AU  - Lu, Xiao
AU  - Guo, Bo
AU  - Zhang, Qingfeng
AU  - Cao, Yaming
AU  - Liu, Taiping
AU  - Cui, Liwang
AU  - Xu, Wenyue
TI  - Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2
AID  - 10.1126/sciadv.aay9269
DP  - 2020 Feb 01
TA  - Science Advances
PG  - eaay9269
VI  - 6
IP  - 9
4099  - http://advances.sciencemag.org/content/6/9/eaay9269.short
4100  - http://advances.sciencemag.org/content/6/9/eaay9269.full
SO  - Sci Adv2020 Feb 01; 6
AB  - 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.