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

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    Authors
    Liehl, Peter
    Chan, Jennie
    Golenbock, Douglas T.
    Fitzgerald, Katherine A.
    Mota, Maria M.
    UMass Chan Affiliations
    Department of Medicine, Division of Infectious Diseases and Immunology
    Document Type
    Journal Article
    Publication Date
    2014-01-01
    Keywords
    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
    Digestive System
    Digestive System Diseases
    Immunity
    Immunology and Infectious Disease
    Immunology of Infectious Disease
    Infectious Disease
    Parasitic Diseases
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    Link to Full Text
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4096771/
    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.
    Source
    Nat Med. 2014 Jan;20(1):47-53. doi: 10.1038/nm.3424. Epub 2013 Dec 22. Link to article on publisher's site
    DOI
    10.1038/nm.3424
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/34966
    PubMed ID
    24362933
    Notes
    Full author list omitted for brevity. For the full list of authors, see article.
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1038/nm.3424
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