Intercellular communication in the innate immune system through the cGAS-STING pathway

2019 ◽  
pp. 1-11 ◽  
Author(s):  
Ramya Nandakumar ◽  
Samuel Joseph Windross ◽  
Søren R. Paludan
Keyword(s):  
Immune System ◽  
Intercellular Communication ◽  
Innate Immune System ◽  
Innate Immune ◽  
Sting Pathway

scholarly journals Attenuation of cGAS/STING activity during mitosis

2020 ◽  
Vol 3 (9) ◽  
pp. e201900636 ◽  
Author(s):  
Brittany L Uhlorn ◽  
Eduardo R Gamez ◽  
Shuaizhi Li ◽  
Samuel K Campos
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cellular Stress ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Mitotic Chromosomes ◽  
Interphase Cells ◽  
Microbial Infections ◽  
Foreign Dna ◽  
Sting Pathway

The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be nonresponsive to chromosomal self-DNA during open mitosis, although specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that whereas cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme’s production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall, our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.

scholarly journals Attenuation of cGAS/STING Activity During Mitosis

2019 ◽  
Author(s):  
Brittany L. Uhlorn ◽  
Eduardo R. Gamez ◽  
Shuaizhi Li ◽  
Samuel K. Campos
Keyword(s):  
Immune System ◽  
Innate Immune System ◽  
Cellular Stress ◽  
Innate Immune ◽  
Regulatory Mechanisms ◽  
Mitotic Chromosomes ◽  
Interphase Cells ◽  
Microbial Infections ◽  
Foreign Dna ◽  
Sting Pathway

The innate immune system recognizes cytosolic DNA associated with microbial infections and cellular stress via the cGAS/STING pathway, leading to activation of phospho-IRF3 and downstream IFN-I and senescence responses. To prevent hyperactivation, cGAS/STING is presumed to be non-responsive to chromosomal self DNA during open mitosis, though specific regulatory mechanisms are lacking. Given a role for the Golgi in STING activation, we investigated the state of the cGAS/STING pathway in interphase cells with artificially vesiculated Golgi and in cells arrested in mitosis. We find that while cGAS activity is impaired through interaction with mitotic chromosomes, Golgi integrity has little effect on the enzyme’s production of cGAMP. In contrast, STING activation in response to either foreign DNA (cGAS-dependent) or exogenous cGAMP is impaired by a vesiculated Golgi. Overall our data suggest a secondary means for cells to limit potentially harmful cGAS/STING responses during open mitosis via natural Golgi vesiculation.

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