Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages
The Japanese encephalitis virus (JEV) is a <i>Culex</i> mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and res...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-03-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/12/3/356 |
| _version_ | 1819012480451477504 |
|---|---|
| author | Zhao-Yang Wang Zi-Da Zhen Dong-Ying Fan Pei-Gang Wang Jing An |
| author_facet | Zhao-Yang Wang Zi-Da Zhen Dong-Ying Fan Pei-Gang Wang Jing An |
| author_sort | Zhao-Yang Wang |
| collection | DOAJ |
| description | The Japanese encephalitis virus (JEV) is a <i>Culex</i> mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV−host interactions. |
| first_indexed | 2024-12-21T01:44:43Z |
| format | Article |
| id | doaj.art-cec49212159e4024b2128bda9228e6ce |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-12-21T01:44:43Z |
| publishDate | 2020-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-cec49212159e4024b2128bda9228e6ce2022-12-21T19:20:03ZengMDPI AGViruses1999-49152020-03-0112335610.3390/v12030356v12030356Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected MacrophagesZhao-Yang Wang0Zi-Da Zhen1Dong-Ying Fan2Pei-Gang Wang3Jing An4Department of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaDepartment of Microbiology, School of Basic Medical Sciences, Capital Medical University, Beijing 100069, ChinaThe Japanese encephalitis virus (JEV) is a <i>Culex</i> mosquito-borne flavivirus and is the pathogenic agent of Japanese encephalitis, which is the most important type of viral encephalitis in the world. Macrophages are a type of pivotal innate immunocyte that serve as sentinels and respond quickly to pathogen invasions. However, some viruses like JEV can hijack macrophages as a refuge for viral replication and immune escape. Despite their crucial involvement in early JEV infection, the transcriptomic landscapes of JEV-infected macrophages are void. Here, by using an in situ JEV infection model, we investigate the transcriptomic alteration of JEV-infected peritoneal macrophages. We found that, upon JEV infection, the macrophages underwent M1 polarization and showed the drastic activation of innate immune and inflammatory pathways. Interestingly, almost all the programmed cell death (PCD) pathways were activated, especially the apoptosis, pyroptosis, and necroptosis pathways, which were verified by the immunofluorescent staining of specific markers. Further transcriptomic analysis and TUNEL staining revealed that JEV infection caused apparent DNA damage. The transcriptomic analysis also revealed that JEV infection promoted ROS and RNS generation and caused oxidative stress, which activated multiple cell death pathways. Our work uncovers the pivotal pathogenic roles of oxidative stress and multiple PCD pathways in JEV infection, providing a novel perspective on JEV−host interactions.https://www.mdpi.com/1999-4915/12/3/356japanese encephalitis virustranscriptomic analysismacrophage polarizationprogrammed cell deathoxidative stress |
| spellingShingle | Zhao-Yang Wang Zi-Da Zhen Dong-Ying Fan Pei-Gang Wang Jing An Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages Viruses japanese encephalitis virus transcriptomic analysis macrophage polarization programmed cell death oxidative stress |
| title | Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages |
| title_full | Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages |
| title_fullStr | Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages |
| title_full_unstemmed | Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages |
| title_short | Transcriptomic Analysis Suggests the M1 Polarization and Launch of Diverse Programmed Cell Death Pathways in Japanese Encephalitis Virus-Infected Macrophages |
| title_sort | transcriptomic analysis suggests the m1 polarization and launch of diverse programmed cell death pathways in japanese encephalitis virus infected macrophages |
| topic | japanese encephalitis virus transcriptomic analysis macrophage polarization programmed cell death oxidative stress |
| url | https://www.mdpi.com/1999-4915/12/3/356 |
| work_keys_str_mv | AT zhaoyangwang transcriptomicanalysissuggeststhem1polarizationandlaunchofdiverseprogrammedcelldeathpathwaysinjapaneseencephalitisvirusinfectedmacrophages AT zidazhen transcriptomicanalysissuggeststhem1polarizationandlaunchofdiverseprogrammedcelldeathpathwaysinjapaneseencephalitisvirusinfectedmacrophages AT dongyingfan transcriptomicanalysissuggeststhem1polarizationandlaunchofdiverseprogrammedcelldeathpathwaysinjapaneseencephalitisvirusinfectedmacrophages AT peigangwang transcriptomicanalysissuggeststhem1polarizationandlaunchofdiverseprogrammedcelldeathpathwaysinjapaneseencephalitisvirusinfectedmacrophages AT jingan transcriptomicanalysissuggeststhem1polarizationandlaunchofdiverseprogrammedcelldeathpathwaysinjapaneseencephalitisvirusinfectedmacrophages |