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Chitin-derived poly...
Chitin-derived polymer deacetylation regulates mitochondrial reactive oxygen species dependent cGAS-STING and NLRP3 inflammasome activation
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- Turley, Joanna (författare)
- Trinity College Dublin, Ireland
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- Moran, Hanna (författare)
- Trinity College Dublin, Ireland
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- McEntee, Craig (författare)
- Trinity College Dublin, Ireland
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- O'Grady, Katie (författare)
- Trinity College Dublin, Ireland
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- Muñoz-Wolf, Natalia (författare)
- Trinity College Dublin, Ireland
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- Jin, Lei (författare)
- University of Florida, USA
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- Follmann, Frank (författare)
- Statens Serum Institute, Denmark
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- Andersen, Peter (författare)
- Statens Serum Institute, Denmark
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- Andersson, Mats (författare)
- RISE
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- Lavelle, Ed (författare)
- Trinity College Dublin, Ireland
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(creator_code:org_t)
- Elsevier Ltd, 2021
- 2021
- Engelska.
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Ingår i: Biomaterials. - : Elsevier Ltd. - 0142-9612 .- 1878-5905. ; 275
- Relaterad länk:
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https://doi.org/10.1...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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)
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Nyckelord
- 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
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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- Av författaren/redakt...
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Turley, Joanna
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Moran, Hanna
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McEntee, Craig
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O'Grady, Katie
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Muñoz-Wolf, Nata ...
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Jin, Lei
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visa fler...
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Follmann, Frank
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Andersen, Peter
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Andersson, Mats
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Lavelle, Ed
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visa färre...
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