TRIM14 Is a Key Regulator of the Type I IFN Response during Mycobacterium tuberculosis Infection. Academic Article uri icon


  • Tripartite motif-containing proteins (TRIMs) play a variety of recently described roles in innate immunity. Although many TRIMs regulate type I 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 an activator of cGAS-dependent cytosolic DNA sensing, we set out to investigate a role for TRIM proteins in regulating macrophage responses to M. tuberculosis In this study, we demonstrate that TRIM14, a noncanonical TRIM that lacks an E3 ubiquitin ligase RING domain, is a critical negative regulator of the type I IFN response in Mus musculus macrophages. We show that TRIM14 interacts with both cGAS and TBK1 and that macrophages lacking TRIM14 dramatically hyperinduce IFN stimulated gene (ISG) expression following M. tuberculosis infection, cytosolic nucleic acid transfection, and IFN- treatment. Consistent with a defect in resolution of the type I IFN response, Trim14 knockout macrophages have more phospho-Ser754 STAT3 relative to phospho-Ser727 and fail to upregulate the STAT3 target Socs3, 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 resolve ISG expression. Remarkably, Trim14 knockout macrophages hyperinduce expression of antimicrobial genes like Nos2 and are significantly better than control cells at limiting M. tuberculosis replication. Collectively, these data reveal an unappreciated role for TRIM14 in resolving type I IFN responses and controlling M. tuberculosis infection.

published proceedings

  • J Immunol

altmetric score

  • 6.25

author list (cited authors)

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

citation count

  • 28

complete list of authors

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

publication date

  • July 2020