Direct type I interferon signaling in hepatocytes controls malaria

Camila Marques-da-Silva, Kristen Peissig, Michael P. Walker, Justine Shiau, Carson Bowers, Dennis E. Kyle, Rahul Vijay, Scott E. Lindner, Samarchith P. Kurup

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Malaria is a devastating disease impacting over half of the world's population. Plasmodium parasites that cause malaria undergo obligatory development and replication in hepatocytes before infecting red blood cells and initiating clinical disease. While type I interferons (IFNs) are known to facilitate innate immune control to Plasmodium in the liver, how they do so has remained unresolved, precluding the manipulation of such responses to combat malaria. Utilizing transcriptomics, infection studies, and a transgenic Plasmodium strain that exports and traffics Cre recombinase, we show that direct type I IFN signaling in Plasmodium-infected hepatocytes is necessary to control malaria. We also show that the majority of infected hepatocytes naturally eliminate Plasmodium infection, revealing the potential existence of anti-malarial cell-autonomous immune responses in such hepatocytes. These discoveries challenge the existing paradigms in Plasmodium immunobiology and are expected to inspire anti-malarial drugs and vaccine strategies.

Original languageEnglish (US)
Article number111098
JournalCell Reports
Volume40
Issue number3
DOIs
StatePublished - Jul 19 2022

All Science Journal Classification (ASJC) codes

  • General Biochemistry, Genetics and Molecular Biology

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