Opposite Responses of Interferon and Proinflammatory Cytokines Induced by Human Metapneumovirus and Respiratory Syncytial Virus in Macrophages

Macrophages are a principal pulmonary source of type I and III interferons (IFNs), initiating and coordinating the early antiviral response to respiratory viral infections. Yet the contribution of macrophage-derived IFNs to host defense during human metapneumovirus (HMPV) infection remains poorly de...

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Bibliographic Details
Main Authors: Iván Martínez-Espinoza, Antonieta Guerrero-Plata
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Pathogens
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Online Access:https://www.mdpi.com/2076-0817/14/7/694
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Summary:Macrophages are a principal pulmonary source of type I and III interferons (IFNs), initiating and coordinating the early antiviral response to respiratory viral infections. Yet the contribution of macrophage-derived IFNs to host defense during human metapneumovirus (HMPV) infection remains poorly defined. Here, we use human primary monocyte-derived macrophages (MDMs) and THP-1-derived macrophages to analyze the IFN responses induced by HMPV compared to its closely related human pneumovirus, respiratory syncytial virus (RSV). We show that HMPV induced a robust response of type I and type III IFNs and ISGs, whereas RSV elicited only a modest, delayed IFN response despite strong IRF activation; instead, RSV preferentially activates NF-κB and exhibits a pronounced proinflammatory cytokine output. Our results highlight the role of macrophages as key modulators of the IFN and proinflammatory responses during HMPV and RSV infection.
ISSN:2076-0817