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Article: Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity

TitleAdenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity
Authors
KeywordsStaphylococcus aureus
T cell responses
NLRP3 inflammasome
Adenosine synthase A
Issue Date2021
PublisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com
Citation
EBioMedicine, 2021, v. 70, p. article no. 103505 How to Cite?
AbstractBackground: Staphylococcus aureus is a common human pathogen capable of causing diverse illnesses with possible recurrent infections. Although recent studies have highlighted the role of cellular immunity in recurrent infections, the mechanism by which S. aureus evades host responses remains largely unexplored. Methods: This study utilizes in vitro and in vivo infection experiments to investigate difference of pro-inflammatory responses and subsequent adaptive immune responses between adsA mutant and WT S. aureus strain infection. Findings: We demonstrated that adenosine synthase A (AdsA), a potent S. aureus virulence factor, can alter Th17 responses by interfering with NLRP3 inflammasome-mediated IL-1β production. Specifically, S. aureus virulence factor AdsA dampens Th1/Th17 immunity by limiting the release of IL-1β and other Th polarizing cytokines. In particular, AdsA obstructs the release of IL-1β via the adenosine/A2aR/NLRP3 axis. Using a murine infection model, pharmacological inhibition of A2a receptor enhanced S. aureus-specific Th17 responses, whereas inhibition of NLRP3 and caspase-1 downregulated these responses. Our results showed that AdsA contributes to recurrent S. aureus infection by restraining protective Th1/Th17 responses. Interpretation: Our study provides important mechanistic insights for therapeutic and vaccination strategies against S. aureus infections. Funding This work was supported by grants from Shenzhen Peacock project (KQTD2015033-117210153), and Guangdong Science and Technology Department (2020B1212030004) to J.H. and China Postdoctoral Science Foundation (2019M663167) to BZZ. We also thank the L & T Charitable Foundation, the Guangdong Science and Technology Department (2020B1212030004), and the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019BT02Y198) for their support.
Persistent Identifierhttp://hdl.handle.net/10722/306275
ISSN
2023 Impact Factor: 9.7
2023 SCImago Journal Rankings: 3.193
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorDENG, J-
dc.contributor.authorZhang, BZ-
dc.contributor.authorChu, H-
dc.contributor.authorWang, XL-
dc.contributor.authorWang, Y-
dc.contributor.authorGong, HR-
dc.contributor.authorLi, R-
dc.contributor.authorYang, D-
dc.contributor.authorLi, C-
dc.contributor.authorDou, Y-
dc.contributor.authorGao, P-
dc.contributor.authorCai, JP-
dc.contributor.authorJin, M-
dc.contributor.authorDu, Q-
dc.contributor.authorChan, JFW-
dc.contributor.authorKao, RYT-
dc.contributor.authorYuen, KY-
dc.contributor.authorHuang, JD-
dc.date.accessioned2021-10-20T10:21:17Z-
dc.date.available2021-10-20T10:21:17Z-
dc.date.issued2021-
dc.identifier.citationEBioMedicine, 2021, v. 70, p. article no. 103505-
dc.identifier.issn2352-3964-
dc.identifier.urihttp://hdl.handle.net/10722/306275-
dc.description.abstractBackground: Staphylococcus aureus is a common human pathogen capable of causing diverse illnesses with possible recurrent infections. Although recent studies have highlighted the role of cellular immunity in recurrent infections, the mechanism by which S. aureus evades host responses remains largely unexplored. Methods: This study utilizes in vitro and in vivo infection experiments to investigate difference of pro-inflammatory responses and subsequent adaptive immune responses between adsA mutant and WT S. aureus strain infection. Findings: We demonstrated that adenosine synthase A (AdsA), a potent S. aureus virulence factor, can alter Th17 responses by interfering with NLRP3 inflammasome-mediated IL-1β production. Specifically, S. aureus virulence factor AdsA dampens Th1/Th17 immunity by limiting the release of IL-1β and other Th polarizing cytokines. In particular, AdsA obstructs the release of IL-1β via the adenosine/A2aR/NLRP3 axis. Using a murine infection model, pharmacological inhibition of A2a receptor enhanced S. aureus-specific Th17 responses, whereas inhibition of NLRP3 and caspase-1 downregulated these responses. Our results showed that AdsA contributes to recurrent S. aureus infection by restraining protective Th1/Th17 responses. Interpretation: Our study provides important mechanistic insights for therapeutic and vaccination strategies against S. aureus infections. Funding This work was supported by grants from Shenzhen Peacock project (KQTD2015033-117210153), and Guangdong Science and Technology Department (2020B1212030004) to J.H. and China Postdoctoral Science Foundation (2019M663167) to BZZ. We also thank the L & T Charitable Foundation, the Guangdong Science and Technology Department (2020B1212030004), and the Program for Guangdong Introducing Innovative and Entrepreneurial Teams (2019BT02Y198) for their support.-
dc.languageeng-
dc.publisherElsevier: Creative Commons. The Journal's web site is located at http://www.ebiomedicine.com-
dc.relation.ispartofEBioMedicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectStaphylococcus aureus-
dc.subjectT cell responses-
dc.subjectNLRP3 inflammasome-
dc.subjectAdenosine synthase A-
dc.titleAdenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity-
dc.typeArticle-
dc.identifier.emailChu, H: hinchu@hku.hk-
dc.identifier.emailWang, XL: xiaoleiw@hku.hk-
dc.identifier.emailYang, D: dongfang@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailDou, Y: douying@hku.hk-
dc.identifier.emailGao, P: gaopeng@hku.hk-
dc.identifier.emailCai, JP: caijuice@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailKao, RYT: rytkao@hkucc.hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailHuang, JD: jdhuang@hku.hk-
dc.identifier.authorityChu, H=rp02125-
dc.identifier.authorityLi, C=rp02783-
dc.identifier.authorityGao, P=rp02794-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityKao, RYT=rp00481-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityHuang, JD=rp00451-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1016/j.ebiom.2021.103505-
dc.identifier.pmid34332295-
dc.identifier.pmcidPMC8340124-
dc.identifier.scopuseid_2-s2.0-85111267194-
dc.identifier.hkuros327280-
dc.identifier.volume70-
dc.identifier.spagearticle no. 103505-
dc.identifier.epagearticle no. 103505-
dc.identifier.isiWOS:000689246500011-
dc.publisher.placeNetherlands-

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