Host-cell sensors for Plasmodium activate innate immunity against liver-stage infection

Peter Liehl, Vanessa Zuzarte-Luís, Jennie Chan, Thomas Zillinger, Fernanda Baptista, Daniel Carapau, Madlen Konert, Kirsten K. Hanson, Céline Carret, Caroline Lassnig, Mathias Müller, Ulrich Kalinke, Mohsan Saeed, Angelo Ferreira Chora, Douglas T. Golenbock, Birgit Strobl, Miguel Prudêncio, Luis P. Coelho, Stefan H. Kappe, Giulio Superti-FurgaAndreas Pichlmair, Ana M. Vigário, Charles M. Rice, Katherine A. Fitzgerald, Winfried Barchet, Maria M. Mota

Research output: Contribution to journalArticlepeer-review

215 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)47-53
Number of pages7
JournalNature Medicine
Volume20
Issue number1
DOIs
StatePublished - 2014
Externally publishedYes

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