TXNIP Regulates Natural Killer Cell-Mediated Innate Immunity by Inhibiting IFN-? Production during Bacterial Infection.

ABSTRACT: The function of natural killer (NK) cell-derived interferon-? (IFN-?) expands to remove pathogens by increasing the ability of innate immune cells. Here, we identified the critical role of thioredoxin-interacting protein (TXNIP) in the production of IFN-? in NK cells during bacterial infection. TXNIP inhibited the production of IFN-? and the activation of transforming growth factor ?-activated kinase 1 (TAK1) activity in primary mouse and human NK cells. TXNIP directly interacted with TAK1 and inhibited TAK1 activity by interfering with the complex formation between TAK1 and TAK1 binding protein 1 (TAB1). Txnip^-/- (KO) NK cells enhanced the activation of macrophages by inducing IFN-? production during Pam3CSK4 stimulation or Staphylococcus aureus (S. aureus) infection and contributed to expedite the bacterial clearance. Our findings suggest that NK cell-derived IFN-? is critical for host defense and that TXNIP plays an important role as an inhibitor of NK cell-mediated macrophage activation by inhibiting the production of IFN-? during bacterial infection.

SUBMITTER: Kim DO 

PROVIDER: S-EPMC7765025 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature