Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity
Background: 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...
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Format: | Article |
Language: | English |
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Elsevier
2021-08-01
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Series: | EBioMedicine |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S235239642100298X |
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doaj-de7cd6d9ac834f5483f3034cef961878 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jian Deng Bao-zhong Zhang Hin Chu Xiao-lei Wang Yixin Wang Hua-Rui Gong Renhao Li Dong Yang Cun Li Ying Dou Peng Gao Jian-piao Cai Meilin Jin Qian Du Jasper Fuk-Woo Chan Richard Yi-Tsun Kao Kwok-Yung Yuen Jian-Dong Huang |
spellingShingle |
Jian Deng Bao-zhong Zhang Hin Chu Xiao-lei Wang Yixin Wang Hua-Rui Gong Renhao Li Dong Yang Cun Li Ying Dou Peng Gao Jian-piao Cai Meilin Jin Qian Du Jasper Fuk-Woo Chan Richard Yi-Tsun Kao Kwok-Yung Yuen Jian-Dong Huang Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity EBioMedicine Staphylococcus aureus T cell responses NLRP3 inflammasome Adenosine synthase A |
author_facet |
Jian Deng Bao-zhong Zhang Hin Chu Xiao-lei Wang Yixin Wang Hua-Rui Gong Renhao Li Dong Yang Cun Li Ying Dou Peng Gao Jian-piao Cai Meilin Jin Qian Du Jasper Fuk-Woo Chan Richard Yi-Tsun Kao Kwok-Yung Yuen Jian-Dong Huang |
author_sort |
Jian Deng |
title |
Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity |
title_short |
Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity |
title_full |
Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity |
title_fullStr |
Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity |
title_full_unstemmed |
Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunity |
title_sort |
adenosine synthase a contributes to recurrent staphylococcus aureus infection by dampening protective immunity |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2021-08-01 |
description |
Background: 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. |
topic |
Staphylococcus aureus T cell responses NLRP3 inflammasome Adenosine synthase A |
url |
http://www.sciencedirect.com/science/article/pii/S235239642100298X |
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doaj-de7cd6d9ac834f5483f3034cef9618782021-07-31T04:40:09ZengElsevierEBioMedicine2352-39642021-08-0170103505Adenosine synthase A contributes to recurrent Staphylococcus aureus infection by dampening protective immunityJian Deng0Bao-zhong Zhang1Hin Chu2Xiao-lei Wang3Yixin Wang4Hua-Rui Gong5Renhao Li6Dong Yang7Cun Li8Ying Dou9Peng Gao10Jian-piao Cai11Meilin Jin12Qian Du13Jasper Fuk-Woo Chan14Richard Yi-Tsun Kao15Kwok-Yung Yuen16Jian-Dong Huang17School of Biomedical Sciences, The University of Hong Kong, Hong Kong, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, ChinaSchool of Biomedical Sciences, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, ChinaCAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, ChinaThe University of Hong Kong-Shenzhen Hospital, Shenzhen, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, ChinaDepartment of Microbiology, The University of Hong Kong, Hong Kong, China; State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China; Corresponding authors.School of Biomedical Sciences, The University of Hong Kong, Hong Kong, China; CAS Key Laboratory of Quantitative Engineering Biology, Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Corresponding authors.Background: 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.http://www.sciencedirect.com/science/article/pii/S235239642100298XStaphylococcus aureusT cell responsesNLRP3 inflammasomeAdenosine synthase A |