STING Recognition of Cytoplasmic DNA Instigates Cellular Defense

Takayuki Abe; Ai Harashima; Tianli Xia; Hiroyasu Konno; Keiko Konno; Alejo Morales; Jeonghyun Ahn; Delia Gutman; Glen N Barber

doi:10.1016/j.molcel.2013.01.039

STING Recognition of Cytoplasmic DNA Instigates Cellular Defense

Takayuki Abe, Ai Harashima, Tianli Xia, Hiroyasu Konno, Keiko Konno, Alejo Morales, Jeonghyun Ahn, Delia Gutman, Glen N Barber

Cell Biology

Research output: Contribution to journal › Article

136 Scopus citations

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	https://doi.org/10.1016/j.molcel.2013.01.039
State	Published - Apr 11 2013

Fingerprint

ASJC Scopus subject areas

Molecular Biology
Cell Biology

Cite this

Abe, T., Harashima, A., Xia, T., Konno, H., Konno, K., Morales, A., Ahn, J., Gutman, D., & Barber, G. N. (2013). STING Recognition of Cytoplasmic DNA Instigates Cellular Defense. Molecular Cell, 50(1), 5-15. https://doi.org/10.1016/j.molcel.2013.01.039

@article{b8337f1828c2422d9bd13d0e23c79580,

title = "STING Recognition of Cytoplasmic DNA Instigates Cellular Defense",

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.",

author = "Takayuki Abe and Ai Harashima and Tianli Xia and Hiroyasu Konno and Keiko Konno and Alejo Morales and Jeonghyun Ahn and Delia Gutman and Barber, {Glen N}",

year = "2013",

month = apr

day = "11",

doi = "10.1016/j.molcel.2013.01.039",

language = "English",

volume = "50",

pages = "5--15",

journal = "Molecular Cell",

issn = "1097-2765",

publisher = "Cell Press",

number = "1",

}

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.

UR - http://www.scopus.com/inward/record.url?scp=84876085954&partnerID=8YFLogxK

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 -

Access to Document

10.1016/j.molcel.2013.01.039