Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response
<i>Human Metapneumovirus</i> (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show tha...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-05-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/8/6/824 |
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| author | Antonella Bugatti Stefania Marsico Manuela Fogli Sara Roversi Serena Messali Daniela Bosisio Cinzia Giagulli Arnaldo Caruso Silvano Sozzani Simona Fiorentini Francesca Caccuri |
| author_facet | Antonella Bugatti Stefania Marsico Manuela Fogli Sara Roversi Serena Messali Daniela Bosisio Cinzia Giagulli Arnaldo Caruso Silvano Sozzani Simona Fiorentini Francesca Caccuri |
| author_sort | Antonella Bugatti |
| collection | DOAJ |
| description | <i>Human Metapneumovirus</i> (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, <i>per se</i>, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment. |
| first_indexed | 2024-03-10T19:29:04Z |
| format | Article |
| id | doaj.art-caa3b87421384f6a8d67cd8cbf6ff0ae |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T19:29:04Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-caa3b87421384f6a8d67cd8cbf6ff0ae2023-11-20T02:17:19ZengMDPI AGMicroorganisms2076-26072020-05-018682410.3390/microorganisms8060824Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune ResponseAntonella Bugatti0Stefania Marsico1Manuela Fogli2Sara Roversi3Serena Messali4Daniela Bosisio5Cinzia Giagulli6Arnaldo Caruso7Silvano Sozzani8Simona Fiorentini9Francesca Caccuri10Section of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalyDepartment of Pharmacy, Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende, 87036 Cosenza, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of General Pathology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of General Pathology and Immunology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, ItalySection of Microbiology, Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy<i>Human Metapneumovirus</i> (HMPV) is a major cause of lower respiratory tract infections. HMPV infection has been hypothesized to alter dendritic cell (DC) immune response; however, many questions regarding HMPV pathogenesis within the infected lung remain unanswered. Here, we show that HMPV productively infects human lung microvascular endothelial cells (L-HMVECs). The release of infectious virus occurs for up to more than 30 days of culture without producing overt cytopathic effects and medium derived from persistently HMPV-infected L-HMVECs (secretome) induced monocyte-derived DCs to prime naïve CD4 T-cells toward a Th2 phenotype. Moreover, we demonstrated that infected secretomes trigger DCs to up-regulate OX40L expression and OX40L neutralization abolished the pro-Th2 effect that is induced by HMPV-secretome. We clarified secretome from HMPV by size exclusion and ultracentrifugation with the aim to characterize the role of viral particles in the observed pro-Th2 effect. In both cases, the percentage of IL-4-producing cells and expression of OX40L returned at basal levels. Finally, we showed that HMPV, <i>per se</i>, could reproduce the ability of secretome to prime pro-Th2 DCs. These results suggest that HMPV, persistently released by L-HMVECs, might take part in the development of a skewed, pro-Th2 lung microenvironment.https://www.mdpi.com/2076-2607/8/6/824<i>human metapneumovirus</i>dendritic cellsTh2 responseIL-4OX40L |
| spellingShingle | Antonella Bugatti Stefania Marsico Manuela Fogli Sara Roversi Serena Messali Daniela Bosisio Cinzia Giagulli Arnaldo Caruso Silvano Sozzani Simona Fiorentini Francesca Caccuri Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response Microorganisms <i>human metapneumovirus</i> dendritic cells Th2 response IL-4 OX40L |
| title | Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response |
| title_full | Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response |
| title_fullStr | Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response |
| title_full_unstemmed | Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response |
| title_short | Human Metapneumovirus Establishes Persistent Infection in Lung Microvascular Endothelial Cells and Primes a Th2-Skewed Immune Response |
| title_sort | human metapneumovirus establishes persistent infection in lung microvascular endothelial cells and primes a th2 skewed immune response |
| topic | <i>human metapneumovirus</i> dendritic cells Th2 response IL-4 OX40L |
| url | https://www.mdpi.com/2076-2607/8/6/824 |
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