Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation
In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolate...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2527 |
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| author | Emilia Nunzi Letizia Mezzasoma Ilaria Bellezza Teresa Zelante Pierluigi Orvietani Giuliana Coata Irene Giardina Krizia Sagini Giorgia Manni Alessandro Di Michele Marco Gargaro Vincenzo N. Talesa Gian Carlo Di Renzo Francesca Fallarino Rita Romani |
| author_facet | Emilia Nunzi Letizia Mezzasoma Ilaria Bellezza Teresa Zelante Pierluigi Orvietani Giuliana Coata Irene Giardina Krizia Sagini Giorgia Manni Alessandro Di Michele Marco Gargaro Vincenzo N. Talesa Gian Carlo Di Renzo Francesca Fallarino Rita Romani |
| author_sort | Emilia Nunzi |
| collection | DOAJ |
| description | In pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells. |
| first_indexed | 2024-03-11T09:40:55Z |
| format | Article |
| id | doaj.art-77d90c8aa7e04bf5b573ec36545f0c2f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:40:55Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-77d90c8aa7e04bf5b573ec36545f0c2f2023-11-16T16:58:35ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243252710.3390/ijms24032527Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome ActivationEmilia Nunzi0Letizia Mezzasoma1Ilaria Bellezza2Teresa Zelante3Pierluigi Orvietani4Giuliana Coata5Irene Giardina6Krizia Sagini7Giorgia Manni8Alessandro Di Michele9Marco Gargaro10Vincenzo N. Talesa11Gian Carlo Di Renzo12Francesca Fallarino13Rita Romani14Department of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Obstetrics and Gynecology, University Hospital of Perugia, Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital, The Norwegian Radium Hospital, 0379 Oslo, NorwayDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Physics and Geology, University of Perugia, Via Pascoli, 06123 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Obstetrics, Gynecology and Perinatology IM Sechenov First State University, 117997 Moscow, RussiaDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyDepartment of Medicine and Surgery, University of Perugia, Polo Unico Sant’Andrea delle Fratte, P.e Lucio Severi 1, 06132 Perugia, ItalyIn pregnancy, human amniotic fluid extracellular vesicles (HAF-EVs) exert anti-inflammatory effects on T cells and on monocytes, supporting their immunoregulatory roles. The specific mechanisms are still not completely defined. The aim of this study was to investigate the ability of HAF-EVs, isolated from pregnant women who underwent amniocentesis and purified by gradient ultracentrifugation, to affect inflammasome activation in the human monocytes. Proteomic studies revealed that HAF-EV samples expressed several immunoregulatory molecules as well as small amounts of endotoxin. Surprisingly, metagenomic analysis shows the presence of specific bacterial strain variants associated with HAF-EVs as potential sources of the endotoxin. Remarkably, we showed that a single treatment of THP-1 cells with HAF-EVs triggered inflammasome activation, whereas the same treatment followed by LPS and ATP sensitization prevented inflammasome activation, a pathway resembling monocyte refractories. A bioinformatics analysis of microbiota-HAF-EVs functional pathways confirmed the presence of enzymes for endotoxin biosynthesis as well as others associated with immunoregulatory functions. Overall, these data suggest that HAF-EVs could serve as a source of the isolation of a specific microbiota during early pregnancy. Moreover, HAF-EVs could act as a novel system to balance immune training and tolerance by modulating the inflammasome in monocytes or other cells.https://www.mdpi.com/1422-0067/24/3/2527extracellular vesiclesamniotic fluidLPSmetagenomic analysis |
| spellingShingle | Emilia Nunzi Letizia Mezzasoma Ilaria Bellezza Teresa Zelante Pierluigi Orvietani Giuliana Coata Irene Giardina Krizia Sagini Giorgia Manni Alessandro Di Michele Marco Gargaro Vincenzo N. Talesa Gian Carlo Di Renzo Francesca Fallarino Rita Romani Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation International Journal of Molecular Sciences extracellular vesicles amniotic fluid LPS metagenomic analysis |
| title | Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation |
| title_full | Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation |
| title_fullStr | Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation |
| title_full_unstemmed | Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation |
| title_short | Microbiota-Associated HAF-EVs Regulate Monocytes by Triggering or Inhibiting Inflammasome Activation |
| title_sort | microbiota associated haf evs regulate monocytes by triggering or inhibiting inflammasome activation |
| topic | extracellular vesicles amniotic fluid LPS metagenomic analysis |
| url | https://www.mdpi.com/1422-0067/24/3/2527 |
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