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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.
Vise andre og tillknytning
2021 (engelsk)Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 275, artikkel-id 120961Artikkel i tidsskrift (Fagfellevurdert) 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)

sted, utgiver, år, opplag, sider
Elsevier Ltd , 2021. Vol. 275, artikkel-id 120961
Emneord [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
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Identifikatorer
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
Merknad

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).

Tilgjengelig fra: 2021-06-30 Laget: 2021-06-30 Sist oppdatert: 2021-06-30bibliografisk kontrollert

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