Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2

Sci Adv. 2020 Feb 26;6(9):eaay9269. doi: 10.1126/sciadv.aay9269. eCollection 2020 Feb.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Female
  • Fibrinogen / genetics
  • Fibrinogen / immunology*
  • Humans
  • Immunity, Innate*
  • Macrophages / immunology*
  • Malaria, Falciparum / genetics
  • Malaria, Falciparum / immunology*
  • Male
  • Mice
  • Mice, Knockout
  • Plasmodium falciparum / genetics
  • Plasmodium falciparum / immunology*
  • Plasmodium falciparum / pathogenicity


  • FGL2 protein, human
  • Fgl2 protein, mouse
  • Fibrinogen