1. Cytoplasmic RNA Sensor Pathways and Nitazoxanide Broadly Inhibit Intracellular Mycobacterium tuberculosis Growth
- Author
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Shahin Ranjbar, Viraga Haridas, Aya Nambu, Luke D. Jasenosky, Supriya Sadhukhan, Thomas S. Ebert, Veit Hornung, Gail H. Cassell, James V. Falvo, and Anne E. Goldfeld
- Subjects
Science - Abstract
Summary: To establish stable infection, Mycobacterium tuberculosis (MTb) must overcome host innate immune mechanisms, including those that sense pathogen-derived nucleic acids. Here, we show that the host cytosolic RNA sensing molecules RIG-I-like receptor (RLR) signaling proteins RIG-I and MDA5, their common adaptor protein MAVS, and the RNA-dependent kinase PKR each independently inhibit MTb growth in human cells. Furthermore, we show that MTb broadly stimulates RIG-I, MDA5, MAVS, and PKR gene expression and their biological activities. We also show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits intracellular MTb growth and amplifies MTb-stimulated RNA sensor gene expression and activity. This study establishes prototypic cytoplasmic RNA sensors as innate restriction factors for MTb growth in human cells and it shows that targeting this pathway is a potential host-directed approach to treat tuberculosis disease. : Biological Sciences; Immunology; Immune Response; Microbiology; Molecular Microbiology Subject Areas: Biological Sciences, Immunology, Immune Response, Microbiology, Molecular Microbiology
- Published
- 2019
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