Human metapneumovirus (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, per se, 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.

Human metapneumovirus establishes persistent infection in lung microvascular endothelial cells and primes a th2-skewed immune response / Bugatti, A.; Marsico, S.; Fogli, M.; Roversi, S.; Messali, S.; Bosisio, D.; Giagulli, C.; Caruso, A.; Sozzani, S.; Fiorentini, S.; Caccuri, F.. - In: MICROORGANISMS. - ISSN 2076-2607. - 8:6(2020). [10.3390/microorganisms8060824]

Human metapneumovirus establishes persistent infection in lung microvascular endothelial cells and primes a th2-skewed immune response

Sozzani S.
Membro del Collaboration Group
;
2020

Abstract

Human metapneumovirus (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, per se, 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.
2020
dendritic cells; human metapneumovirus; IL-4; OX40L; Th2 response
01 Pubblicazione su rivista::01a Articolo in rivista
Human metapneumovirus establishes persistent infection in lung microvascular endothelial cells and primes a th2-skewed immune response / Bugatti, A.; Marsico, S.; Fogli, M.; Roversi, S.; Messali, S.; Bosisio, D.; Giagulli, C.; Caruso, A.; Sozzani, S.; Fiorentini, S.; Caccuri, F.. - In: MICROORGANISMS. - ISSN 2076-2607. - 8:6(2020). [10.3390/microorganisms8060824]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1475187
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