Unknown

Dataset Information

0

Deficiency of the AIM2-ASC Signal Uncovers the STING-Driven Overreactive Response of Type I IFN and Reciprocal Depression of Protective IFN-? Immunity in Mycobacterial Infection.


ABSTRACT: The nucleic acids of Mycobacterium tuberculosis can be detected by intracellular DNA sensors, such as cyclic GMP-AMP synthase and absent in melanoma 2 (AIM2), which results in the release of type I IFN and the proinflammatory cytokine IL-1?. However, whether cross-talk occurs between AIM2-IL-1? and cyclic GMP-AMP synthase-type I IFN signaling upon M. tuberculosis infection in vivo is unclear. In this article, we demonstrate that mycobacterial infection of AIM2-/- mice reciprocally induces overreactive IFN-? and depressive IFN-? responses, leading to higher infection burdens and more severe pathology. We also describe the underlying mechanism whereby activated apoptosis-associated speck-like protein interacts with a key adaptor, known as stimulator of IFN genes (STING), and inhibits the interaction between STING and downstream TANK-binding kinase 1 in bone marrow-derived macrophages and bone marrow-derived dendritic cells, consequently reducing the induction of type I IFN. Of note, apoptosis-associated speck-like protein expression is inversely correlated with IFN-? levels in PBMCs from tuberculosis patients. These data demonstrate that the AIM2-IL-1? signaling pathway negatively regulates the STING-type I IFN signaling pathway by impeding the association between STING and TANK-binding kinase 1, which protects the host from M. tuberculosis infection. This finding has potential clinical significance.

SUBMITTER: Yan S 

PROVIDER: S-EPMC6309432 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

altmetric image

Publications

Deficiency of the AIM2-ASC Signal Uncovers the STING-Driven Overreactive Response of Type I IFN and Reciprocal Depression of Protective IFN-γ Immunity in Mycobacterial Infection.

Yan Shanshan S   Shen Hongbo H   Lian Qiaoshi Q   Jin Wenlong W   Zhang Ronghua R   Lin Xuan X   Gu Wangpeng W   Sun Xiaoyu X   Meng Guangxun G   Tian Zhigang Z   Chen Zheng W ZW   Sun Bing B  

Journal of immunology (Baltimore, Md. : 1950) 20171218 3


The nucleic acids of <i>Mycobacterium tuberculosis</i> can be detected by intracellular DNA sensors, such as cyclic GMP-AMP synthase and absent in melanoma 2 (AIM2), which results in the release of type I IFN and the proinflammatory cytokine IL-1β. However, whether cross-talk occurs between AIM2-IL-1β and cyclic GMP-AMP synthase-type I IFN signaling upon <i>M. tuberculosis</i> infection in vivo is unclear. In this article, we demonstrate that mycobacterial infection of AIM2<sup>-/-</sup> mice re  ...[more]

Similar Datasets

| S-EPMC8402087 | biostudies-literature
| S-EPMC6603966 | biostudies-literature
| S-EPMC3507439 | biostudies-literature
| S-EPMC3879373 | biostudies-literature
| S-EPMC7451475 | biostudies-literature
| S-EPMC5834677 | biostudies-literature
| S-EPMC3386939 | biostudies-literature
| S-EPMC4258479 | biostudies-literature
| S-EPMC8300883 | biostudies-literature