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Chitin-derived polymer deacetylation regulates mitochondrial reactive oxygen species dependent cGAS-STING and NLRP3 inflammasome activation
Trinity College Dublin, Ireland.
Trinity College Dublin, Ireland.
Trinity College Dublin, Ireland.
Trinity College Dublin, Ireland.
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2021 (English)In: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 275, article id 120961Article in journal (Refereed) Published
Abstract [en]

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)

Place, publisher, year, edition, pages
Elsevier Ltd , 2021. Vol. 275, article id 120961
Keywords [en]
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
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:ri:diva-54697DOI: 10.1016/j.biomaterials.2021.120961Scopus ID: 2-s2.0-85108354865OAI: oai:DiVA.org:ri-54697DiVA, id: diva2:1575635
Note

Funding details: Science Foundation Ireland, SFI, 12/1A/1421, 19/FFP/6484; Funding text 1: This work was suppored by Science Foundation Ireland awards to the Lavelle lab (12/1A/1421, 19/FFP/6484).

Available from: 2021-06-30 Created: 2021-06-30 Last updated: 2021-06-30Bibliographically approved

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