Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection, Nature Immunology, Published online 02 March 2015
发布时间：2015年03月03日
Nature Immunology, Published online 02 March 2015, DOI: doi:10.1038/ni.3117
Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection
Pengyan Xia, Shuo Wang, Buqing Ye, Ying Du, Guanling Huang, Pingping Zhu & Zusen 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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Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection, Nature Immunology, Published online 02 March 2015
Nature Immunology, Published online 02 March 2015, DOI: doi:10.1038/ni.3117
Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection
Pengyan Xia, Shuo Wang, Buqing Ye, Ying Du, Guanling Huang, Pingping Zhu & Zusen 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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文章链接：http://www.nature.com/ni/journal/vaop/ncurrent/full/ni.3117.html