Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages

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

Research output: Contribution to journalArticle

67 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Innate Immunity
Liver
Interferons
Malaria
Parasites
Interferon Type I
Natural Killer T-Cells
T-cells
Infection
Interferon alpha-beta Receptor
Interferon Regulatory Factor-3
Cell signaling
RNA Sequence Analysis
Culicidae
Coinfection
Hepatocytes
Rodentia
Cell Count
RNA

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages. / Miller, Jessica L.; Wilder, Brandon; Baldwin, Michael; Vaughan, Ashley M.; Kappe, Stefan H.I.

In: Cell Reports, Vol. 7, No. 2, 24.04.2014, p. 436-447.

Research output: Contribution to journalArticle

Miller, Jessica L. ; Wilder, Brandon ; Baldwin, Michael ; Vaughan, Ashley M. ; Kappe, Stefan H.I. / Interferon-Mediated Innate Immune Responses against Malaria Parasite Liver Stages. In: Cell Reports. 2014 ; Vol. 7, No. 2. pp. 436-447.
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