Sox2 functions as a sequence-specific DNA sensor in neutrophils to initiate innate immunity against microbial infection.
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.
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pengyan
P
Xia
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Shuo
S
Wang
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Buqing
B
Ye
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Ying
Y
Du
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Guanling
G
Huang
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Pingping
P
Zhu
Key Laboratory of Infection and Immunity of CAS, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Zusen
Z
Fan
D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D000818:Animals; D003593:Cytoplasm / Q000276:immunology / Q000382:microbiology; D004269:DNA, Bacterial / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D008089:Listeria monocytogenes / Q000276:immunology; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000401:mortality; D020930:MAP Kinase Kinase Kinases / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D055503:Protein Multimerization; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D016019:Survival Analysis; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000276:immunology; D000099151:MAP Kinase Kinase Kinase 7
D048868:Adaptor Proteins, Signal Transducing; D004269:DNA, Bacterial; D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D055748:SOXB1 Transcription Factors; D051193:Toll-Like Receptors; D018808:Transcription Factor AP-1; D000099151:MAP Kinase Kinase Kinase 7; C527783:Sox2 protein, mouse; C498761:Tab2 protein, mouse