Diverse intracellular pathogens activate type III interferon expression from peroxisomes

 Charlotte Odendall, Evelyn Dixit, Fabrizia Stavru, Helene Bierne, Kate M Franz, Ann Fiegen Durbin, Steeve Boulant, Lee Gehrke, Pascale Cossart & Jonathan C Kagan

Nature Immunology 15,717–726(2014)

Speaker: Li-Chun Wang (王立君)             Time: 14:00~15:00, Nov 26, 2014

Commentator: Dr. Chia-Yi Yu (余佳益 老師)   Place: Room 601

Abstract:

Type I interferons are considered the classic pathway via type I interferon receptors to induce interferon-stimulated genes (ISGs) that reveal diverse antiviral responses in mammals. However, previous studies show that several pathogens activate antiviral responses in the absence of type I interferons. Currently known that type III interferons are antiviral cytokines with type I IFN-like biological functions¹. Nevertheless, the mechanism by which type III interferon responses are induced remains unclear. Previous study found that a mitochondrial adaptor MAVS/IPS-1 acting downstream of RIG-I like receptors (RLRs), was also located on peroxisomes to induce antiviral responses. In this study, they first identified that cytokines induced by MAVS signaling from peroxisomes activated of the JAK-STAT1 pathway  leading to expression of ISGs to produce antiviral responses. Subsequently, they found that RLRs induced type III interferon expression in a variety of human cells, and identified differential regulation of type I and type III interferons. Upon detecting viral RNA, RLRs engaged with the peroxisomal MAVS to drive type III interferon response. In addition, some transcription factors such as IRF1, IRF3, IRF7, NF-κB were shown to involve in type III interferon expression. They also found that during the natural process of epithelial cell differentiation and polarization, expression of type III interferons was associated with the abundance of peroxisomes. Taken together, author revealed the importance of peroxisome in regulating type III interferon expression. Corresponding to this aspect, persons who have defective peroxisomes may suffer from diverse intracellular pathogen infection.

References：

1.         Iversen MB, Paludan SR. Mechanisms of type III interferon expression. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 2010, 30(8): 573-578.