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Spotlight on Innate Immune Science, August 2020: STING and COPA Syndrome; Inflammasome Activation in COVID-19 Patients
In this new monthly series, our scientific advisors break down the latest research and trends in innate immune system science from leading publications and institutions.
COPA Syndrome and the STING Pathway
Summary:. COPA syndrome is a complex, autoinflammatory disease like lupus or polyarthritis, and patients with this disease have constitutive activation of the STING pathway. The disease is due to the missense mutations in the COPA gene, which lead to a mis-sorting of proteins transitioning between the Golgi and the endoplasmic reticulum (ER) of a cell. In the first study, authors found COPA function leads to enhanced type I interferon signaling due to a failure of Golgi-to-ER STING retrieval. The second study demonstrated that COPA maintains immune homeostasis by regulating STING transport at the Golgi, which could contribute to immune dysregulation in COPA syndrome.
So What: COPA syndrome joins a growing list of human genetic diseases (including SAVI and AGS) that are caused by aberrant activation of the STING pathway. Currently, there are no approved treatments or cures for COPA syndrome. With knowledge from this study, COPA syndrome patients could benefit from STING inhibitors, and research could lead to potential, early proof of concept clinical indication.
Read More in: Mutations in COPA lead to abnormal trafficking of STING to the Golgi and interferon signaling and A defect in COPI-mediated transport of 1 STING causes immune dysregulation in COPA syndrome
New Study Reinforces Link Between NLRP3 Inflammasome and COVID-19
Summary: Researchers at the University of São Paulo demonstrated that the NLRP3 inflammasome not only becomes activated in response to the SARS-CoV-2 coronavirus, but also influences clinical outcomes in COVID-19 patients. The study published in medRxiv examined moderate and severe COVID-19 patients as well as noted NLRP3 inflammasome activity in post-mortem patients. Inflammasomes like NLRP3 are innate immune system receptors and sensors that regulate the activation of inflammatory enzymes such as caspase-1 and induce inflammation. In sera taken from blood samples of patients, inflammasome-derived biproducts like Casp1p20 correlated with the markers of COVID-19 severity. The research team infected primary human monocytes in vitro with SARS-CoV-2 and assessed inflammasome activation while also looking at inflammasome activation in lung tissues obtained from autopsies of deceased COVID-19 patients. Data demonstrated that the inflammasome is more robustly active in COVID-19 patients with severe cases.
So What: These conclusions suggest the use of inflammasome activation both as a marker of disease for severity and also as a potential therapeutic target for COVID-19. More studies on NLRP3 and other pathways of the innate immune system will advance our understanding of COVID-19 and potentially other coronaviruses, helping inform better treatments and, potentially, cures.
Read More in:Inflammasome activation in COVID-19 patients
Stay tuned next month for additional studies and perspectives shared by the IFM R&D Team!