| First Author | Marques-da-Silva C | Year | 2025 |
| Journal | Cell Host Microbe | Volume | 33 |
| Issue | 4 | Pages | 529-544.e9 |
| PubMed ID | 40168996 | Mgi Jnum | J:365978 |
| Mgi Id | MGI:8189359 | Doi | 10.1016/j.chom.2025.03.008 |
| Citation | Marques-da-Silva C, et al. (2025) Type I interferons induce guanylate-binding proteins and lysosomal defense in hepatocytes to control malaria. Cell Host Microbe 33(4):529-544.e9 |
| abstractText | Plasmodium parasites undergo development and replication within hepatocytes before infecting erythrocytes and initiating clinical malaria. Although type I interferons (IFNs) are known to hinder Plasmodium infection within the liver, the underlying mechanisms remain unclear. Here, we describe two IFN-I-driven hepatocyte antimicrobial programs controlling liver-stage malaria. First, oxidative defense by NADPH oxidases 2 and 4 triggers a pathway of lysosomal fusion with the parasitophorous vacuole (PV) to help clear Plasmodium. Second, guanylate-binding protein (GBP) 1-mediated disruption of the PV activates the caspase-1 inflammasome, inducing pyroptosis to remove infected host cells. Remarkably, both human and mouse hepatocytes enlist these cell-autonomous immune programs to eliminate Plasmodium, with their pharmacologic or genetic inhibition leading to profound malarial susceptibility in vivo. In addition to identifying IFN-I-mediated cell-autonomous immune circuits controlling Plasmodium infection in the hepatocytes, our study also extends the understanding of how non-immune cells are integral to protective immunity against malaria. |
