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

• Main Authors: Dong Oh Kim, Jae-Eun Byun, Won Sam Kim, Mi Jeong Kim, Jung Ha Choi, Hanna Kim, Eunji Choi, Tae-Don Kim, Suk Ran Yoon, Ji-Yoon Noh, Young-Jun Park, Jungwoon Lee, Hee Jun Cho, Hee Gu Lee, Sang-Hyun Min, Inpyo Choi, Haiyoung Jung
• Format: Article
• Language: English
• Published: MDPI AG 2020-12-01
• Series: International Journal of Molecular Sciences
• Subjects: NK cell; IFN-γ; TXNIP; TAK1; toll-like receptor (TLR); bacterial infection
• Online Access: https://www.mdpi.com/1422-0067/21/24/9499
• ISSN: 1661-6596; 1422-0067

The function of natural killer (NK) cell-derived interferon-γ (IFN-γ) 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-γ in NK cells during bacterial infection. TXNIP inhibited the production of IFN-γ and the activation of transforming growth factor β-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). <i>Txnip</i>^−/− (KO) NK cells enhanced the activation of macrophages by inducing IFN-γ production during Pam3CSK4 stimulation or Staphylococcus aureus (<i>S. aureus</i>) infection and contributed to expedite the bacterial clearance. Our findings suggest that NK cell-derived IFN-γ 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-γ during bacterial infection.