Interferon-Independent Activities of Mammalian STING Mediate Antiviral Response and Tumor Immune Evasion.
Immunity
; 53(1): 115-126.e5, 2020 07 14.
Article
em En
| MEDLINE
| ID: mdl-32640258
ABSTRACT
Type I interferon (IFN) response is commonly recognized as the main signaling activity of STING. Here, we generate the Sting1S365A/S365A mutant mouse that precisely ablates IFN-dependent activities while preserving IFN-independent activities of STING. StingS365A/S365A mice protect against HSV-1 infection, despite lacking the STING-mediated IFN response. This challenges the prevailing view and suggests that STING controls HSV-1 infection through IFN-independent activities. Transcriptomic analysis reveals widespread IFN-independent activities of STING in macrophages and T cells, and STING activities in T cells are predominantly IFN independent. In mouse tumor models, T cells in the tumor experience substantial cell death that is in part mediated by IFN-independent activities of STING. We found that the tumor induces STING-mediated cell death in T cells to evade immune control. Our data demonstrate that mammalian STING possesses widespread IFN-independent activities that are important for restricting HSV-1 infection, tumor immune evasion and likely also adaptive immunity.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferon Tipo I
/
Herpesvirus Humano 1
/
Evasão Tumoral
/
Proteínas de Membrana
/
Neoplasias
Limite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Immunity
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Estados Unidos