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Updated: Aug 16, 2026

High-throughput Quantitative Real-time RT-PCR Assay for Determining Expression Profiles of Types I and III Interferon Subtypes
Published on: March 24, 2015
Strong, sustained type I IFN signaling acts cell intrinsically to impair IFNγ responses and cause tuberculosis
Stefan A Fattinger1, Bianca Parisi2, Roberto A Chavez3
1Division of Immunology and Molecular Medicine, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
Abstract:
Mycobacterium tuberculosis (Mtb) causes over one million deaths annually, but most infected individuals never exhibit symptoms. Type I interferons (IFNs) have emerged as a major factor driving susceptibility to Mtb, but how type I IFNs impair immunity to Mtb is a key unresolved question. Here, we show that an early effect of type I IFN during Mtb infection is the cell-intrinsic impairment of IFNγ signaling. IFNγ signaling is selectively impaired in the subset of infected macrophages experiencing high and sustained levels of type I IFN signaling. Genetic elimination of regulated stimulator of interferon via stabilization of transcript (RESIST), a recently described positive regulator of type I IFN production, specifically eliminates the high and sustained type I IFN response, fully restores IFNγ signaling, and rescues susceptibility to Mtb without affecting basal type I IFN responses. Our results demonstrate that strong and sustained type I IFN responses specifically and cell intrinsically impair responsiveness to IFNγ to cause susceptibility to Mtb.
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