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Bleomycin-Induced Lung Injury Increases Resistance to Influenza Virus Infection in a Type I Interferon-Dependent Manner

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Abstract
Acute lung injury (ALI) results in acute respiratory disease that causes fatal respiratory diseases; however, little is known about the incidence of influenza infection in ALI. Using a ALI-mouse model, we investigated the pro-inflammatory cytokine response to ALI and influenza infection. Mice treated with bleomycin (BLM), which induces ALI, were more resistant to influenza virus infection and exhibited higher levels of type I interferon (IFN-I) transcription during the early infection period than that in PBS-treated control mice. BLM-treated mice also exhibited a lower viral burden, reduced pro-inflammatory cytokine production, and neutrophil levels. In contrast, BLM-treated IFN-I receptor 1 (IFNAR1)-knockout mice failed to show this attenuated phenotype, indicating that IFN-I is key to the antiviral response in ALI-induced mice. The STING/TBK1/IRF3 pathway was found to be involved in IFN-I production and the establishment of an antiviral environment in the lung. The depletion of plasmacytoid dendritic cells (pDCs) reduced the effect of BLM treatment against influenza virus infection, suggesting that pDCs are the major source of IFN-I and are crucial for defense against viral infection in BLM-induced lung injury. Overall, this study showed that BLM-mediated ALI in mice induced the release of double-stranded DNA, which in turn potentiated IFN-I-dependent pulmonary viral resistance by activating the STING/TBK1/IRF3 pathway in association with pDCs.
Author(s)
서상욱정재현백범서최제민최연수고현정권미나
Issued Date
2021
Type
Article
Keyword
acute lung injurypulmonary fibrosisinfluenza virusplasmacytoid dendritic cellstype I interferon
DOI
10.3389/fimmu.2021.697162
URI
https://oak.ulsan.ac.kr/handle/2021.oak/7317
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_aac5e73db63245e3922b5a876de20989&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Bleomycin-Induced%20Lung%20Injury%20Increases%20Resistance%20to%20Influenza%20Virus%20Infection%20in%20a%20Type%20I%20Interferon-Dependent%20Manner&offset=0&pcAvailability=true
Publisher
FRONTIERS IN IMMUNOLOGY
Location
스위스
Language
영어
ISSN
1664-3224
Citation Volume
12
Citation Start Page
0
Citation End Page
0
Appears in Collections:
Medicine > Medicine
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