RT Journal Article
SR Electronic
T1 Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaay9269
DO 10.1126/sciadv.aay9269
VO 6
IS 9
A1 Fu, Yong
A1 Ding, Yan
A1 Wang, Qinghui
A1 Zhu, Feng
A1 Tan, Yulong
A1 Lu, Xiao
A1 Guo, Bo
A1 Zhang, Qingfeng
A1 Cao, Yaming
A1 Liu, Taiping
A1 Cui, Liwang
A1 Xu, Wenyue
YR 2020
UL http://advances.sciencemag.org/content/6/9/eaay9269.abstract
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.