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

Kim, Dong Oh; Byun, Jae-Eun; Kim, Won Sam; Kim, Mi Jeong; Choi, Jung Ha; Kim, Hanna; Choi, Eunji; Kim, Tae-Don; Yoon, Suk Ran; Noh, Ji-Yoon; Park, Young-Jun; Lee, Jungwoon; Cho, Hee Jun; Lee, Hee Gu; Min, Sang-Hyun; Choi, Inpyo; Jung, Haiyoung

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). Txnip−/− (KO) NK cells enhanced the activation of macrophages by inducing IFN-γ 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-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.

BACTERIAL diseases; CELLULAR immunity; NATURAL immunity; PERITONEAL macrophages; KILLER cells; TRANSFORMING growth factors

International Journal of Molecular Sciences, 2020, Vol 21, Issue 24, p9499

1661-6596

Academic Journal

10.3390/ijms21249499