Induction of Interferon-Stimulated Genes by IRF3 Promotes Replication of Toxoplasma gondii (PLoS Pathog 11(3):e1004779, 2015)

報告日期: 2015/10/13
報告時間: 5:10/6:00
報告學生: 黃建銘
講評老師: 辛致煒
附件下載: 下載[1501-1443053459-1.pdf] 

Induction of Interferon-Stimulated Genes by IRF3 Promotes Replication of Toxoplasma gondii

Tanmay Majumdar, Saurabh Chattopadhyay, Evgeny Ozhegov, Jayeeta Dhar, Ramansu Goswami, Ganes C. Sen, Sailen Barik

PLoS Pathog (2015) 11(3): e1004779

Speaker: Jian-Ming Huang (黃建銘)                    Time: 17:00~18:00, Oct. 13, 2015

Commentator: Dr. Jyh-wei shin (辛致煒 老師)     Place: Room 602

 

Abstract:

        Toxoplasma gondii is an intracelluar and parasitic protozoan that causes the disease toxoplasmosis. By and large, T. gondii is capable of infecting virtually all warm-blooded animals like humans. To infect new host cells, T. gondii first escapes from the parasitophorous vacuole and other limiting membranes of the currently infected cell. Although most infections in humans are asymptomatic, the parasite can produce devastating disease such as retino-choroiditis, hydrocephalus, convulsions and intracerebral calcification [1]. Therefore, it is important for the authors to realize pathogenesis including innate immune response of the host against T. gondii. Previous studies showed that Interferon Regulatory Factor 3 (IRF3) is an important transcription factor for the expression of antiviral genes, including type I IFNs and ISGs which leading to the inhibition of one or multiple steps of viral life cycle[2]. However, the authors observed that induction of Interferon-Stimulated Genes (ISGs) by IRF3 promotes replication of T. gondii. To determine the signaling pathway that activates IRF3 in response to parasite infection, the authors observed that Parasite-IRF3 Signaling Activation (PISA) activated IRF3 with the presence of cGAS, STING, and TBK1 instead of the Toll-like receptor or RIG-I-like receptor pathways. Moreover, unlike WT mice, the IRF3-/- mice did not support replication of the parasite and were resistant to pathogenesis caused by T. gondii. In conclusion, the authors found that a new paradigm in which the antiviral host factor, IRF3, plays a cell-intrinsic pro-parasitic role.

References:

  1. Wong, S.Y. and J.S. Remington, Toxoplasmosis in pregnancy. Clin Infect Dis, 1994. 18(6): p. 853-61; quiz 862.
  2. Grandvaux, N., et al., Transcriptional profiling of interferon regulatory factor 3 target genes: direct involvement in the regulation of interferon-stimulated genes. Journal of virology, 2002. 76(11): p. 5532-5539.