Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection.
Peter LiehlVanessa Zuzarte-LuísJennie ChanThomas ZillingerFernanda BaptistaDaniel CarapauMadlen KonertKirsten K HansonCéline CarretCaroline LassnigMathias MüllerUlrich KalinkeMohsan SaeedAngelo Ferreira ChoraDouglas T GolenbockBirgit StroblMiguel PrudêncioLuis P CoelhoStefan H KappeGiulio Superti-FurgaAndreas PichlmairAna M VigárioCharles M RiceKatherine A FitzgeraldWinfried BarchetMaria M MotaPublished in: Nature medicine (2013)
Before they infect red blood cells and cause malaria, Plasmodium parasites undergo an obligate and clinically silent expansion phase in the liver that is supposedly undetected by the host. Here, we demonstrate the engagement of a type I interferon (IFN) response during Plasmodium replication in the liver. We identified Plasmodium RNA as a previously unrecognized pathogen-associated molecular pattern (PAMP) capable of activating a type I IFN response via the cytosolic pattern recognition receptor Mda5. This response, initiated by liver-resident cells through the adaptor molecule for cytosolic RNA sensors, Mavs, and the transcription factors Irf3 and Irf7, is propagated by hepatocytes in an interferon-α/β receptor-dependent manner. This signaling pathway is critical for immune cell-mediated host resistance to liver-stage Plasmodium infection, which we find can be primed with other PAMPs, including hepatitis C virus RNA. Together, our results show that the liver has sensor mechanisms for Plasmodium that mediate a functional antiparasite response driven by type I IFN.
Keyphrases
- plasmodium falciparum
- dendritic cells
- signaling pathway
- hepatitis c virus
- immune response
- induced apoptosis
- transcription factor
- human immunodeficiency virus
- red blood cell
- social media
- stem cells
- bone marrow
- oxidative stress
- hiv infected
- epithelial mesenchymal transition
- mesenchymal stem cells
- single molecule
- endoplasmic reticulum stress
- low cost