Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium

J Immunol. 2018 Oct 15;201(8):2441-2451. doi: 10.4049/jimmunol.1800908. Epub 2018 Sep 12.

Abstract

Baculovirus (BV), an enveloped insect virus with a circular dsDNA genome, possesses unique characteristics that induce strong innate immune responses in mammalian cells. In this study, we show that BV administration in BALB/c mice not only provides complete protection against a subsequent Plasmodium berghei sporozoite infection for up to 7 d after the injection but also eliminates existing liver-stage parasites completely. The elimination of sporozoites by BV was superior to that by primaquine, and this effect occurred in a TLR9-independent manner. At 6 h after BV administration, IFN-α and IFN-γ were robustly produced in the serum, and RNA transcripts of IFN-stimulated genes were markedly upregulated in the liver compared with control mice. The in vivo passive transfer of serum after BV administration effectively eliminated liver-stage parasites, and IFN-α neutralization abolished this effect, indicating that the BV liver-stage parasite-killing mechanism is downstream of the type I IFN signaling pathway. These findings provide evidence that BV-induced, fast-acting innate immunity completely kills liver-stage parasites and, thus, may lead to new malaria drug and vaccine strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baculoviridae / physiology*
  • Cells, Cultured
  • Cytotoxicity, Immunologic
  • Immunity, Innate
  • Immunotherapy, Adoptive / methods*
  • Interferon Type I / metabolism
  • Interferon-alpha / blood
  • Interferon-gamma / blood
  • Liver / immunology*
  • Liver / parasitology
  • Malaria / drug therapy
  • Malaria / immunology*
  • Malaria Vaccines / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / immunology*
  • Primaquine / therapeutic use
  • Signal Transduction
  • Sporozoites

Substances

  • Interferon Type I
  • Interferon-alpha
  • Malaria Vaccines
  • Interferon-gamma
  • Primaquine