Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages

Jessica L. Miller, Brandon K. Sack, Michael Baldwin, Ashley M. Vaughan, Stefan H.I. Kappe

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Mosquito-transmitted malaria parasites infect hepatocytes and asymptomatically replicate as liver stages. Using RNA sequencing, we show that a rodent malaria liver-stage infection stimulates a robust innate immune response including type I interferon (IFN) and IFNγ pathways. Liver-stage infection is suppressed by these infection-engendered innate responses. This suppression was abrogated in mice deficient in IFNγ, the type I IFN α/β receptor (IFNAR), and interferon regulatory factor 3. Natural killer and CD49b+CD3+ natural killer T (NKT) cells increased in the liver after a primary infection, and CD1d-restricted NKT cells, which secrete IFNγ, were critical in reducing liver-stage burden of a secondary infection. Lack of IFNAR signaling abrogated the increase in NKT cell numbers in the liver, showing a link between type I IFN signaling, cell recruitment, and subsequent parasite elimination. Our findings demonstrate innate immune sensing of malaria parasite liver-stage infection and that the ensuing innate responses can eliminate the parasite.

Original languageEnglish (US)
Pages (from-to)436-447
Number of pages12
JournalCell Reports
Volume7
Issue number2
DOIs
StatePublished - Apr 24 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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