Title

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

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

1-2014

Document Type

Article

Subjects

Adaptor Proteins, Signal Transducing; Animals; Blotting, Western; DEAD-box RNA Helicases; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Gene Expression Profiling; Green Fluorescent Proteins; Immunity, Innate; Immunohistochemistry; Interferon Regulatory Factor-3; Interferon Regulatory Factor-7; Interferon Type I; Liver; Luciferases; Mice; Mice, Inbred C57BL; Mice, Transgenic; Microarray Analysis; Oligonucleotides; Plasmodium; Real-Time Polymerase Chain Reaction; Signal Transduction; Statistics, Nonparametric

Disciplines

Digestive System | Digestive System Diseases | Immunity | Immunology and Infectious Disease | Immunology of Infectious Disease | Infectious Disease | Parasitic Diseases

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-alpha/beta 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.

Rights and Permissions

Citation: Nat Med. 2014 Jan;20(1):47-53. doi: 10.1038/nm.3424. Epub 2013 Dec 22. Link to article on publisher's site

Journal/Book/Conference Title

Nature medicine

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

24362933