Osborne Suzanne E, Sit Brandon, Shaker Andrew, Currie Elissa, Tan Joël M J, van Rijn Jorik, Higgins Darren E, Brumell John H
Cell Biology Program, Hospital for Sick Children, Toronto, Ontario, Canada.
Department of Immunology, University of Toronto, Toronto, Ontario, Canada.
Cell Microbiol. 2017 Mar;19(3). doi: 10.1111/cmi.12660. Epub 2016 Oct 10.
Type I interferons (IFNs) play a critical role in antiviral immune responses, but can be deleterious to the host during some bacterial infections. Listeria monocytogenes (Lm) induces a type I IFN response by activating cytosolic antiviral surveillance pathways. This is beneficial to the bacteria as mice lacking the type I IFN receptor (IFNAR1 ) are resistant to systemic infection by Lm. The mechanisms by which type I IFNs promote Lm infection are unclear. Here, we show that IFNAR1 is required for dissemination of Lm within infection foci in livers of infected mice and for efficient cell-to-cell spread in vitro in macrophages. IFNAR1 promotes ActA polarization and actin-based motility in the cytosol of host cells. Our studies suggest type I IFNs directly impact the intracellular life cycle of Lm and provide new insight into the mechanisms used by bacterial pathogens to exploit the type I IFN response.
I型干扰素（IFNs）在抗病毒免疫反应中发挥关键作用，但在某些细菌感染期间可能对宿主有害。单核细胞增生李斯特菌（Lm）通过激活胞质抗病毒监测途径诱导I型干扰素反应。这对细菌有益，因为缺乏I型干扰素受体（IFNAR1）的小鼠对Lm的全身感染具有抗性。I型干扰素促进Lm感染的机制尚不清楚。在这里，我们表明IFNAR1是Lm在受感染小鼠肝脏感染灶内扩散以及在体外巨噬细胞中有效细胞间传播所必需的。IFNAR1促进宿主细胞胞质中ActA极化和基于肌动蛋白的运动。我们的研究表明I型干扰素直接影响Lm的细胞内生命周期，并为细菌病原体利用I型干扰素反应的机制提供了新的见解。
