TRIM14 is a key regulator of the type I interferon response during Mycobacterium tuberculosis infection Institutional Repository Document uri icon


  • ABSTRACTTripartite motif-containing proteins (TRIMs) play a variety of recently described roles in innate immunity. While many TRIMs regulate type I interferon (IFN) expression following cytosolic nucleic acid sensing of viruses, their contribution to innate immune signaling and gene expression during bacterial infection remains largely unknown. Because Mycobacterium tuberculosis is a potent activator of cGAS-dependent cytosolic DNA sensing, we set out to investigate a role for TRIM proteins in regulating macrophage responses to M. tuberculosis. Here we demonstrate that TRIM14, a non-canonical TRIM that lacks an E3 ligase RING domain, is a critical negative regulator of the type I IFN response in macrophages. We show that TRIM14 physically interacts with both cGAS and TBK1 and that macrophages lacking TRIM14 dramatically hyperinduce interferon stimulated gene (ISG) expression following cytosolic nucleic acid transfection, IFN- treatment, and M. tuberculosis infection. Consistent with a defect in resolution of the type I IFN response, Trim14 knockout (KO) macrophages have more phospho-Ser754 STAT3 relative to phospho-727 and fail to upregulate the STAT3 target Socs3 (Suppressor of Cytokine Signaling 3), which is required to turn off IFNAR signaling. These data support a model whereby TRIM14 acts as a scaffold between TBK1 and STAT3 to promote phosphorylation of STAT3 at Ser727 and enhance negative regulation of ISG expression. Remarkably, Trim14 KO macrophages hyperinduce antimicrobials like Inos2 and are significantly better than control cells at limiting M. tuberculosis replication. Collectively, these data reveal a previously unappreciated role for TRIM14 in resolving type I IFN responses and controlling M. tuberculosis infection.

altmetric score

  • 7.9

author list (cited authors)

  • Hoffpauir, C. T., Bell, S. L., West, K. O., Jing, T., Torres-Odio, S., Cox, J. S., ... Watson, R. O.

citation count

  • 4

complete list of authors

  • Hoffpauir, Caitlyn T||Bell, Samantha L||West, Kelsi O||Jing, Tao||Torres-Odio, Sylvia||Cox, Jeffery S||West, A Phillip||Li, Pingwei||Patrick, Kristin L||Watson, Robert O

Book Title

  • bioRxiv

publication date

  • November 2019