Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3
Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to as...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-05-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/78601 |
| _version_ | 1797804144077045760 |
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| author | Rémi Porte Rita Silva-Gomes Charlotte Theroude Raffaella Parente Fatemeh Asgari Marina Sironi Fabio Pasqualini Sonia Valentino Rosanna Asselta Camilla Recordati Marta Noemi Monari Andrea Doni Antonio Inforzato Carlos Rodriguez-Gallego Ignacio Obando Elena Colino Barbara Bottazzi Alberto Mantovani |
| author_facet | Rémi Porte Rita Silva-Gomes Charlotte Theroude Raffaella Parente Fatemeh Asgari Marina Sironi Fabio Pasqualini Sonia Valentino Rosanna Asselta Camilla Recordati Marta Noemi Monari Andrea Doni Antonio Inforzato Carlos Rodriguez-Gallego Ignacio Obando Elena Colino Barbara Bottazzi Alberto Mantovani |
| author_sort | Rémi Porte |
| collection | DOAJ |
| description | Streptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3−/− mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection. |
| first_indexed | 2024-03-13T05:32:44Z |
| format | Article |
| id | doaj.art-993209bc5bb54e2b9ca5713414a9b446 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-13T05:32:44Z |
| publishDate | 2023-05-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-993209bc5bb54e2b9ca5713414a9b4462023-06-14T15:56:36ZengeLife Sciences Publications LtdeLife2050-084X2023-05-011210.7554/eLife.78601Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3Rémi Porte0https://orcid.org/0000-0001-8311-0202Rita Silva-Gomes1Charlotte Theroude2Raffaella Parente3Fatemeh Asgari4Marina Sironi5Fabio Pasqualini6Sonia Valentino7Rosanna Asselta8Camilla Recordati9Marta Noemi Monari10Andrea Doni11Antonio Inforzato12Carlos Rodriguez-Gallego13Ignacio Obando14https://orcid.org/0000-0002-4516-1735Elena Colino15Barbara Bottazzi16https://orcid.org/0000-0002-1930-9257Alberto Mantovani17IRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyInfectious Diseases Service Laboratory, Department of Medicine, Lausanne University Hospital, University Hospital of Lausanne, Lausanne, SwitzerlandIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyMouse and Animal Pathology Laboratory, Fondazione Filarete, Milan, Italy; Department of Veterinary Medicine, University of Milan, Lodi, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, ItalyDepartment of Clinical Sciences, University Fernando Pessoa Canarias, Las Palmas de Gran Canaria, SpainDepartment of Pediatrics, Hospital Universitario Virgen del Rocío, Sevilla, SpainDepartment of Pediatrics, Complejo Hospitalario Universitario Insular Materno Infantil, Las Palmas de Gran Canaria, SpainIRCCS Humanitas Research Hospital, Milan, ItalyIRCCS Humanitas Research Hospital, Milan, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy; William Harvey Research Institute, Queen Mary University of London, London, United KingdomStreptococcus pneumoniae is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the Ptx3 gene expression. Ptx3−/− mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, Ptx3-deficient mice showed enhanced recruitment of neutrophils and inflammation. Using P-selectin-deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, PTX3 gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.https://elifesciences.org/articles/78601Streptococcus pneumoniaePentraxin 3neutrophilsinflammationP-selectinendothelial cells |
| spellingShingle | Rémi Porte Rita Silva-Gomes Charlotte Theroude Raffaella Parente Fatemeh Asgari Marina Sironi Fabio Pasqualini Sonia Valentino Rosanna Asselta Camilla Recordati Marta Noemi Monari Andrea Doni Antonio Inforzato Carlos Rodriguez-Gallego Ignacio Obando Elena Colino Barbara Bottazzi Alberto Mantovani Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 eLife Streptococcus pneumoniae Pentraxin 3 neutrophils inflammation P-selectin endothelial cells |
| title | Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 |
| title_full | Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 |
| title_fullStr | Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 |
| title_full_unstemmed | Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 |
| title_short | Regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin PTX3 |
| title_sort | regulation of inflammation and protection against invasive pneumococcal infection by the long pentraxin ptx3 |
| topic | Streptococcus pneumoniae Pentraxin 3 neutrophils inflammation P-selectin endothelial cells |
| url | https://elifesciences.org/articles/78601 |
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