Abstract
How the cell recognizes cytosolic DNA including DNA-based microbes to trigger host-defense-related gene activation remains to be fully resolved. Here, we demonstrate that STING (stimulator of interferon genes), an endoplasmic reticulum translocon-associated transmembrane protein, acts to detect cytoplasmic DNA species. STING homodimers were able to complex with self- (apoptotic, necrotic) or pathogen-related ssDNA and dsDNA and were indispensible for HSV-1-mediated transcriptional activation of a wide array of innate immune and proinflammatory genes in addition to type I IFN. Our data indicate that STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. In contrast, chronic STING activation may manifest inflammatory responses and possibly autoimmune disease triggered by self-DNA.
| Original language | English |
|---|---|
| Pages (from-to) | 5-15 |
| Number of pages | 11 |
| Journal | Molecular Cell |
| Volume | 50 |
| Issue number | 1 |
| DOIs | |
| State | Published - Apr 11 2013 |
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ASJC Scopus subject areas
- Molecular Biology
- Cell Biology
Cite this
STING Recognition of Cytoplasmic DNA Instigates Cellular Defense. / Abe, Takayuki; Harashima, Ai; Xia, Tianli; Konno, Hiroyasu; Konno, Keiko; Morales, Alejo; Ahn, Jeonghyun; Gutman, Delia; Barber, Glen N.
In: Molecular Cell, Vol. 50, No. 1, 11.04.2013, p. 5-15.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - STING Recognition of Cytoplasmic DNA Instigates Cellular Defense
AU - Abe, Takayuki
AU - Harashima, Ai
AU - Xia, Tianli
AU - Konno, Hiroyasu
AU - Konno, Keiko
AU - Morales, Alejo
AU - Ahn, Jeonghyun
AU - Gutman, Delia
AU - Barber, Glen N
PY - 2013/4/11
Y1 - 2013/4/11
N2 - How the cell recognizes cytosolic DNA including DNA-based microbes to trigger host-defense-related gene activation remains to be fully resolved. Here, we demonstrate that STING (stimulator of interferon genes), an endoplasmic reticulum translocon-associated transmembrane protein, acts to detect cytoplasmic DNA species. STING homodimers were able to complex with self- (apoptotic, necrotic) or pathogen-related ssDNA and dsDNA and were indispensible for HSV-1-mediated transcriptional activation of a wide array of innate immune and proinflammatory genes in addition to type I IFN. Our data indicate that STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. In contrast, chronic STING activation may manifest inflammatory responses and possibly autoimmune disease triggered by self-DNA.
AB - How the cell recognizes cytosolic DNA including DNA-based microbes to trigger host-defense-related gene activation remains to be fully resolved. Here, we demonstrate that STING (stimulator of interferon genes), an endoplasmic reticulum translocon-associated transmembrane protein, acts to detect cytoplasmic DNA species. STING homodimers were able to complex with self- (apoptotic, necrotic) or pathogen-related ssDNA and dsDNA and were indispensible for HSV-1-mediated transcriptional activation of a wide array of innate immune and proinflammatory genes in addition to type I IFN. Our data indicate that STING instigates cytoplasmic DNA-mediated cellular defense gene transcription and facilitates adoptive responses that are required for protection of the host. In contrast, chronic STING activation may manifest inflammatory responses and possibly autoimmune disease triggered by self-DNA.
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UR - http://www.scopus.com/inward/citedby.url?scp=84876085954&partnerID=8YFLogxK
U2 - 10.1016/j.molcel.2013.01.039
DO - 10.1016/j.molcel.2013.01.039
M3 - Article
C2 - 23478444
AN - SCOPUS:84876085954
VL - 50
SP - 5
EP - 15
JO - Molecular Cell
JF - Molecular Cell
SN - 1097-2765
IS - 1
ER -