Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection

Nature Immunology
Pengyan XiaZusen Fan

Abstract

Neutrophils express Toll-like receptors (TLRs) for the recognition of conserved bacterial elements to initiate antimicrobial responses. However, whether other cytosolic DNA sensors are expressed by neutrophils remains elusive. Here we found constitutive expression of the transcription factor Sox2 in the cytoplasm of mouse and human neutrophils. Neutrophil-specific Sox2 deficiency exacerbated bacterial infection. Sox2 directly recognized microbial DNA through its high-mobility-group (HMG) domain. Upon challenge with bacterial DNA, Sox2 dimerization was needed to activate a complex of the kinase TAK1 and its binding partner TAB2, which led to activation of the transcription factors NF-κB and AP-1 in neutrophils. Deficiency in TAK1 or TAB2 impaired Sox2-mediated antibacterial immunity. Overall, we reveal a previously unrecognized role for Sox2 as a cytosolic sequence-specific DNA sensor in neutrophils, which might provide potential therapeutic strategies for the treatment of infectious diseases.

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Citations

Nov 18, 2015·The Journal of Experimental Medicine·Pengyan XiaZusen Fan
Apr 29, 2015·Cellular & Molecular Immunology·Zhou YuXuetao Cao
Apr 9, 2016·Pathogens and Disease·Si Ming ManThirumala-Devi Kanneganti
May 31, 2016·Nature Structural & Molecular Biology·Pingping ZhuZusen Fan
Aug 16, 2016·Seminars in Cell & Developmental Biology·Linlin HouRalf Jauch
Sep 7, 2016·Frontiers in Cell and Developmental Biology·Jacopo BurrelloGiovanni Camussi
Nov 1, 2016·Protein & Cell·Pengyan XiaZusen Fan
Nov 8, 2016·Cellular & Molecular Immunology·Juan Liu, Xuetao Cao
Feb 2, 2017·Annual Review of Immunology·Romain BanchereauVirginia Pascual
Jun 8, 2017·Nature Communications·Pengyan XiaZusen Fan
Nov 27, 2016·Science China. Life Sciences·Yue Zhang, Chunli Liang
Mar 20, 2015·Nature Immunology·Arun K Mankan, Veit Hornung
Dec 5, 2017·AIMS Allergy and Immunology·Ling Wang, Shunbin Ning
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Feb 20, 2018·Cellular & Molecular Immunology·Wei-Wei Luo, Hong-Bing Shu
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Oct 31, 2017·Oxidative Medicine and Cellular Longevity·Tai-Yu ZhaiYi-Hua Sun
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