| First Author | Fu Y | Year | 2020 |
| Journal | Sci Adv | Volume | 6 |
| Issue | 9 | Pages | eaay9269 |
| PubMed ID | 32133407 | Mgi Jnum | J:287601 |
| Mgi Id | MGI:6415459 | Doi | 10.1126/sciadv.aay9269 |
| Citation | Fu Y, et al. (2020) Blood-stage malaria parasites manipulate host innate immune responses through the induction of sFGL2. Sci Adv 6(9):eaay9269 |
| abstractText | 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. |
