Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity

Extracellular vesicles (EVs) released from bacteria are enclosed particles carrying biological active molecules. They have been shown to play a role in bacterial communications and delivery of virulence factors to the host cells. Staphylococcus aureus is an opportunistic pathogen causing a variety o...

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Main Authors: Krisana Asano, Shouhei Hirose, Kouji Narita, Phawinee Subsomwong, Noriaki Kawai, Rojana Sukchawalit, Akio Nakane
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2021.1991239
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author Krisana Asano
Shouhei Hirose
Kouji Narita
Phawinee Subsomwong
Noriaki Kawai
Rojana Sukchawalit
Akio Nakane
author_facet Krisana Asano
Shouhei Hirose
Kouji Narita
Phawinee Subsomwong
Noriaki Kawai
Rojana Sukchawalit
Akio Nakane
author_sort Krisana Asano
collection DOAJ
description Extracellular vesicles (EVs) released from bacteria are enclosed particles carrying biological active molecules. They have been shown to play a role in bacterial communications and delivery of virulence factors to the host cells. Staphylococcus aureus is an opportunistic pathogen causing a variety of infections ranging from impetigo to septicaemia. The EVs released from S. aureus have a high potential to be used for vaccine development against S. aureus infections. However, it is important to clearly understand the impact of SaEVs on the host’s immune response. Our study demonstrated that purified EVs from a clinical isolated methicillin-resistant S. aureus (SaEVs) significantly stimulated proinflammatory cytokine production in mouse immune cells and induced host cell death. An impairment of cytokine production in the Toll-like receptor (TLR)-silenced macrophages suggested that SaEVs stimulate proinflammatory response via TLRs 2, 4 and 9. In mouse infection model, the results demonstrated that SaEV immunization did not provide protective effect. In contrast, all SaEV-immunized mice died within Day 1 after methicillin-resistant S. aureus (MRSA) infection. After MRSA infection for 3 h, the production of IL-6, TNF-α and IL-17 in the spleen of SaEV-immunized mice was significantly higher than that of control mice. On Day 5 after the second immunization, total IgE in the serum was significantly enhanced, and a high titre of Th2-related cytokines was remarkably induced after ex vivo stimulation of the spleen cells with SaEVs. These results suggested that MRSA-derived EVs act as an immunostimulant that induces inflammatory response and IgE-mediated hypersensitivity after MRSA infection.
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spelling doaj.art-1e6eaefd7a974a8181424825ec7ef5082022-12-22T01:33:58ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-011012000200910.1080/22221751.2021.1991239Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivityKrisana Asano0Shouhei Hirose1Kouji Narita2Phawinee Subsomwong3Noriaki Kawai4Rojana Sukchawalit5Akio Nakane6Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanDepartment of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanDepartment of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanDepartment of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanDepartment of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanLaboratory of Biotechnology, Chulabhorn Research Institute, Lak Si, Bangkok, ThailandDepartment of Biopolymer and Health Science, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, JapanExtracellular vesicles (EVs) released from bacteria are enclosed particles carrying biological active molecules. They have been shown to play a role in bacterial communications and delivery of virulence factors to the host cells. Staphylococcus aureus is an opportunistic pathogen causing a variety of infections ranging from impetigo to septicaemia. The EVs released from S. aureus have a high potential to be used for vaccine development against S. aureus infections. However, it is important to clearly understand the impact of SaEVs on the host’s immune response. Our study demonstrated that purified EVs from a clinical isolated methicillin-resistant S. aureus (SaEVs) significantly stimulated proinflammatory cytokine production in mouse immune cells and induced host cell death. An impairment of cytokine production in the Toll-like receptor (TLR)-silenced macrophages suggested that SaEVs stimulate proinflammatory response via TLRs 2, 4 and 9. In mouse infection model, the results demonstrated that SaEV immunization did not provide protective effect. In contrast, all SaEV-immunized mice died within Day 1 after methicillin-resistant S. aureus (MRSA) infection. After MRSA infection for 3 h, the production of IL-6, TNF-α and IL-17 in the spleen of SaEV-immunized mice was significantly higher than that of control mice. On Day 5 after the second immunization, total IgE in the serum was significantly enhanced, and a high titre of Th2-related cytokines was remarkably induced after ex vivo stimulation of the spleen cells with SaEVs. These results suggested that MRSA-derived EVs act as an immunostimulant that induces inflammatory response and IgE-mediated hypersensitivity after MRSA infection.https://www.tandfonline.com/doi/10.1080/22221751.2021.1991239Staphylococcus aureusmethicillin resistancemembrane vesiclesinflammatory stimulationIgE-mediated hypersensitivity
spellingShingle Krisana Asano
Shouhei Hirose
Kouji Narita
Phawinee Subsomwong
Noriaki Kawai
Rojana Sukchawalit
Akio Nakane
Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
Emerging Microbes and Infections
Staphylococcus aureus
methicillin resistance
membrane vesicles
inflammatory stimulation
IgE-mediated hypersensitivity
title Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
title_full Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
title_fullStr Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
title_full_unstemmed Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
title_short Extracellular vesicles from methicillin resistant Staphylococcus aureus stimulate proinflammatory cytokine production and trigger IgE-mediated hypersensitivity
title_sort extracellular vesicles from methicillin resistant staphylococcus aureus stimulate proinflammatory cytokine production and trigger ige mediated hypersensitivity
topic Staphylococcus aureus
methicillin resistance
membrane vesicles
inflammatory stimulation
IgE-mediated hypersensitivity
url https://www.tandfonline.com/doi/10.1080/22221751.2021.1991239
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