Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages
Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children and immuno-compromised individuals. RSV triggers transforming growth factor-beta(TGF-beta) production from lung epithelial cells and TGF-beta...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-12-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00174/full |
| _version_ | 1818132847654862848 |
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| author | Swechha Pokharel Niraj Shil Santanu Bose |
| author_facet | Swechha Pokharel Niraj Shil Santanu Bose |
| author_sort | Swechha Pokharel |
| collection | DOAJ |
| description | Human respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children and immuno-compromised individuals. RSV triggers transforming growth factor-beta(TGF-beta) production from lung epithelial cells and TGF-beta facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-beta and the role of TGF-beta if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-beta and as a consequence these cells activate TGF-beta dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-beta production from RSV infected macrophages. In an effort to elucidate the role of TGF-beta and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-beta---SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g. interferon-beta or IFN-beta) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-beta---SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-beta. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-beta. Thus, our studies have unfolded the requirement of autophagy---TGF-beta---SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages. |
| first_indexed | 2024-12-11T08:43:20Z |
| format | Article |
| id | doaj.art-6fb9727e2afb4263a6ba7ddffcf184de |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-11T08:43:20Z |
| publishDate | 2016-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-6fb9727e2afb4263a6ba7ddffcf184de2022-12-22T01:14:13ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882016-12-01610.3389/fcimb.2016.00174234300Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophagesSwechha Pokharel0Niraj Shil1Santanu Bose2Washington State UniversityWashington State UniversityWashington State UniversityHuman respiratory syncytial virus (RSV) is a lung tropic virus causing severe airway diseases including bronchiolitis and pneumonia among infants, children and immuno-compromised individuals. RSV triggers transforming growth factor-beta(TGF-beta) production from lung epithelial cells and TGF-beta facilitates RSV infection of these cells. However, it is still unknown whether RSV infected myeloid cells like macrophages produce TGF-beta and the role of TGF-beta if any during RSV infection of these cells. Our study revealed that RSV infected macrophages produce TGF-beta and as a consequence these cells activate TGF-beta dependent SMAD-2/3 signaling pathway. Further mechanistic studies illustrated a role of autophagy in triggering TGF-beta production from RSV infected macrophages. In an effort to elucidate the role of TGF-beta and SMAD-2/3 signaling during RSV infection, we surprisingly unfolded the requirement of TGF-beta---SMAD2/3 signaling in conferring optimal innate immune antiviral response during RSV infection of macrophages. Type-I interferon (e.g. interferon-beta or IFN-beta) is a critical host factor regulating innate immune antiviral response during RSV infection. Our study revealed that loss of TGF-beta---SMAD2/3 signaling pathway in RSV infected macrophages led to diminished expression and production of IFN-beta. Inhibiting autophagy in RSV infected macrophages also resulted in reduced production of IFN-beta. Thus, our studies have unfolded the requirement of autophagy---TGF-beta---SMAD2/3 signaling network for optimal innate immune antiviral response during RSV infection of macrophages.http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00174/fullAutophagyInterferon-betaMacrophagesTGF-betaSmadrespiratory syncytial virus |
| spellingShingle | Swechha Pokharel Niraj Shil Santanu Bose Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages Frontiers in Cellular and Infection Microbiology Autophagy Interferon-beta Macrophages TGF-beta Smad respiratory syncytial virus |
| title | Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages |
| title_full | Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages |
| title_fullStr | Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages |
| title_full_unstemmed | Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages |
| title_short | Autophagy, TGF-beta and SMAD-2/3 signaling regulates interferon-beta response in respiratory syncytial virus infected macrophages |
| title_sort | autophagy tgf beta and smad 2 3 signaling regulates interferon beta response in respiratory syncytial virus infected macrophages |
| topic | Autophagy Interferon-beta Macrophages TGF-beta Smad respiratory syncytial virus |
| url | http://journal.frontiersin.org/Journal/10.3389/fcimb.2016.00174/full |
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