First Author | Emran TB | Year | 2018 |
Journal | J Immunol | Volume | 201 |
Issue | 8 | Pages | 2441-2451 |
PubMed ID | 30209187 | Mgi Jnum | J:266184 |
Mgi Id | MGI:6203246 | Doi | 10.4049/jimmunol.1800908 |
Citation | Emran TB, et al. (2018) Baculovirus-Induced Fast-Acting Innate Immunity Kills Liver-Stage Plasmodium. J Immunol 201(8):2441-2451 |
abstractText | 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-alpha and IFN-gamma 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-alpha 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. |