Chitin-derived polymer deacetylation regulates mitochondrial reactive oxygen species dependent cGAS-STING and NLRP3 inflammasome activation
| العنوان: | Chitin-derived polymer deacetylation regulates mitochondrial reactive oxygen species dependent cGAS-STING and NLRP3 inflammasome activation |
|---|---|
| المؤلفون: | Turley, Joanna, Moran, Hanna, McEntee, Craig, O'Grady, Katie, Muñoz-Wolf, Natalia, Jin, Lei, Follmann, Frank, Andersen, Peter, Andersson, Mats, Lavelle, Ed |
| المصدر: | Biomaterials. 275 |
| مصطلحات موضوعية: | Chitosan, IFNAR, Mitochondrial stress, NLRP3, STING, Vaccine adjuvant, Acetylation, Antigens, Biocompatibility, Chemical activation, Oxygen, Vaccines, Cationic polysaccharide, Deacetylation, Degree of deacetylation, Inflammasome, Reactive oxygen species, Vaccine adjuvants |
| الوصف: | Chitosan is a cationic polysaccharide that has been evaluated as an adjuvant due to its biocompatible and biodegradable nature. The polysaccharide can enhance antibody responses and cell-mediated immunity following vaccination by injection or mucosal routes. However, the optimal polymer characteristics for activation of dendritic cells (DCs) and induction of antigen-specific cellular immune responses have not been resolved. Here, we demonstrate that only chitin-derived polymers with a high degree of deacetylation (DDA) enhance generation of mitochondrial reactive oxygen species (mtROS), leading to cGAS-STING mediated induction of type I IFN. Additionally, the capacity of the polymers to activate the NLRP3 inflammasome was strictly dependent on the degree and pattern of deacetylation and mtROS generation. Polymers with a DDA below 80% are poor adjuvants while a fully deacetylated polyglucosamine polymer is most effective as a vaccine adjuvant. Furthermore, this polyglucosamine polymer enhanced antigen-specific Th1 responses in a NLRP3 and STING-type I IFN-dependent manner. Overall these results indicate that the degree of chitin deacetylation, the acetylation pattern and its regulation of mitochondrial ROS are the key determinants of its immune enhancing effects. © 2021 The Author(s) |
| وصف الملف: | |
| الوصول الحر: | https://urn.kb.se/resolve?urn=urn:nbn:se:ri:diva-54697Test https://doi.org/10.1016/j.biomaterials.2021.120961Test |
| قاعدة البيانات: | SwePub |
| تدمد: | 01429612 18785905 |
|---|---|
| DOI: | 10.1016/j.biomaterials.2021.120961 |