PMID- 32133407
OWN - NLM
STAT- MEDLINE
DCOM- 20201112
LR  - 20201112
IS  - 2375-2548 (Electronic)
IS  - 2375-2548 (Linking)
VI  - 6
IP  - 9
DP  - 2020 Feb
TI  - Blood-stage malaria parasites manipulate host innate immune responses through the 
      induction of sFGL2.
PG  - eaay9269
LID - 10.1126/sciadv.aay9269 [doi]
LID - eaay9269
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-gamma. sFGL2 inhibited c-Jun N-terminal 
      kinase phosphorylation in the Toll-like receptor 2 signaling pathway of 
      macrophages dependent on FcgammaRIIB 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.
CI  - Copyright (c) 2020 The Authors, some rights reserved; exclusive licensee American 
      Association for the Advancement of Science. No claim to original U.S. Government 
      Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 
      (CC BY-NC).
FAU - Fu, Yong
AU  - Fu Y
AUID- ORCID: 0000-0001-6480-1147
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Ding, Yan
AU  - Ding Y
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Wang, Qinghui
AU  - Wang Q
AD  - Department of Immunology, College of Basic Medical Sciences, China Medical 
      University, Shenyang, Liaoning, P.R. China.
FAU - Zhu, Feng
AU  - Zhu F
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Tan, Yulong
AU  - Tan Y
AUID- ORCID: 0000-0002-9296-8064
AD  - Department of Tropical Medicine, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Lu, Xiao
AU  - Lu X
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Guo, Bo
AU  - Guo B
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Zhang, Qingfeng
AU  - Zhang Q
AD  - Research Center for Translational Medicine, Key Laboratory of Arrhythmias of the 
      Ministry of Education of China, East Hospital, Tongji University School of 
      Medicine, Shanghai, P.R. China.
FAU - Cao, Yaming
AU  - Cao Y
AD  - Department of Immunology, College of Basic Medical Sciences, China Medical 
      University, Shenyang, Liaoning, P.R. China.
FAU - Liu, Taiping
AU  - Liu T
AUID- ORCID: 0000-0003-2261-1155
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
FAU - Cui, Liwang
AU  - Cui L
AUID- ORCID: 0000-0002-8338-1974
AD  - Department of Internal Medicine, Morsani College of Medicine, University of South 
      Florida, Tampa, FL 33612, USA.
FAU - Xu, Wenyue
AU  - Xu W
AUID- ORCID: 0000-0003-3681-5052
AD  - Department of Pathogenic Biology, Army Medical University (The Third Military 
      Medical University), Chongqing 400038, P.R. China.
LA  - eng
GR  - U19 AI089672/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200226
PL  - United States
TA  - Sci Adv
JT  - Science advances
JID - 101653440
RN  - 0 (FGL2 protein, human)
RN  - 0 (Fgl2 protein, mouse)
RN  - 9001-32-5 (Fibrinogen)
SB  - IM
MH  - Animals
MH  - Female
MH  - Fibrinogen/genetics/*immunology
MH  - Humans
MH  - *Immunity, Innate
MH  - Macrophages/*immunology
MH  - Malaria, Falciparum/genetics/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Plasmodium falciparum/genetics/*immunology/pathogenicity
PMC - PMC7043914
EDAT- 2020/03/07 06:00
MHDA- 2020/11/13 06:00
PMCR- 2020/02/26
CRDT- 2020/03/06 06:00
PHST- 2019/07/30 00:00 [received]
PHST- 2019/12/05 00:00 [accepted]
PHST- 2020/03/06 06:00 [entrez]
PHST- 2020/03/07 06:00 [pubmed]
PHST- 2020/11/13 06:00 [medline]
PHST- 2020/02/26 00:00 [pmc-release]
AID - aay9269 [pii]
AID - 10.1126/sciadv.aay9269 [doi]
PST - epublish
SO  - Sci Adv. 2020 Feb 26;6(9):eaay9269. doi: 10.1126/sciadv.aay9269. eCollection 2020 
      Feb.