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Bacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages

Identifieur interne : 000725 ( Pmc/Curation ); précédent : 000724; suivant : 000726

Bacterial Outer Membrane Vesicles Provide Broad-Spectrum Protection against Influenza Virus Infection via Recruitment and Activation of Macrophages

Auteurs : Eun-Hye Bae [Corée du Sud] ; Sang Hwan Seo [Corée du Sud] ; Chang-Ung Kim [Corée du Sud] ; Min Seong Jang [Corée du Sud] ; Min-Suk Song [Corée du Sud] ; Tae-Young Lee [Corée du Sud] ; Yu-Jin Jeong [Corée du Sud] ; Moo-Seung Lee [Corée du Sud] ; Jong-Hwan Park [Corée du Sud] ; Pureum Lee [Corée du Sud] ; Young Sang Kim [Corée du Sud] ; Sang-Hyun Kim [Corée du Sud] ; Doo-Jin Kim [Corée du Sud]

Source :

RBID : PMC:6738265

Abstract

Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle ­harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.


Url:
DOI: 10.1159/000494098
PubMed: 30844806
PubMed Central: 6738265

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PMC:6738265

Le document en format XML

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<p>Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle ­harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.</p>
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<name>
<surname>Bae</surname>
<given-names>Eun-Hye</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<name>
<surname>Seo</surname>
<given-names>Sang Hwan</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<name>
<surname>Kim</surname>
<given-names>Chang-Ung</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
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<surname>Jang</surname>
<given-names>Min Seong</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
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<surname>Song</surname>
<given-names>Min-Suk</given-names>
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<sup>c</sup>
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<surname>Lee</surname>
<given-names>Tae-Young</given-names>
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<sup>a</sup>
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<name>
<surname>Jeong</surname>
<given-names>Yu-Jin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Moo-Seung</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Park</surname>
<given-names>Jong-Hwan</given-names>
</name>
<xref ref-type="aff" rid="aff4">
<sup>d</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Lee</surname>
<given-names>Pureum</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Young Sang</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Sang-Hyun</given-names>
</name>
<xref ref-type="aff" rid="aff6">
<sup>f</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Kim</surname>
<given-names>Doo-Jin</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>a</sup>
</xref>
<xref ref-type="aff" rid="aff2">
<sup>b</sup>
</xref>
<xref ref-type="aff" rid="aff5">
<sup>e</sup>
</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>a</sup>
Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, Republic of Korea</aff>
<aff id="aff2">
<sup>b</sup>
Department of Biochemistry, Chungnam National University, Daejeon, Republic of Korea</aff>
<aff id="aff3">
<sup>c</sup>
College of Medicine and Medical Research Institute, Chungbuk National University, Cheongju, Republic of Korea</aff>
<aff id="aff4">
<sup>d</sup>
College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea</aff>
<aff id="aff5">
<sup>e</sup>
University of Science and Technology (UST), Daejeon, Republic of Korea</aff>
<aff id="aff6">
<sup>f</sup>
College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea</aff>
<author-notes>
<corresp id="cor1">*Prof. Sang-Hyun Kim, College of Veterinary Medicine, Gyeongsang National University, 501 Jinjudae-ro, Jinju 52828 (South Korea), E-Mail vetmicro@gnu.ac.kr, Dr. Doo-Jin Kim, Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), 125 Gwahak-ro, Daejeon 34141 (South Korea), E-Mail
<email>golddj@kribb.re.kr</email>
</corresp>
<fn fn-type="other">
<p>Eun-Hye Bae and Sang Hwan Seo contributed equally to this work.</p>
</fn>
</author-notes>
<pub-date pub-type="ppub">
<month>6</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="epub">
<day>7</day>
<month>3</month>
<year>2019</year>
</pub-date>
<pub-date pub-type="pmc-release">
<day>7</day>
<month>3</month>
<year>2019</year>
</pub-date>
<pmc-comment> PMC Release delay is 0 months and 0 days and was based on the . </pmc-comment>
<volume>11</volume>
<issue>4</issue>
<fpage>316</fpage>
<lpage>329</lpage>
<history>
<date date-type="received">
<day>16</day>
<month>5</month>
<year>2018</year>
</date>
<date date-type="accepted">
<day>16</day>
<month>9</month>
<year>2018</year>
</date>
<date date-type="subscription-year">
<year>2019</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright © 2019 by S. Karger AG, Basel</copyright-statement>
<copyright-year>2019</copyright-year>
</permissions>
<abstract>
<p>Influenza A virus (IAV) poses a constant worldwide threat to human health. Although conventional vaccines are available, their protective efficacy is type or strain specific, and their production is time-consuming. For the control of an influenza pandemic in particular, agents that are immediately effective against a wide range of virus variants should be developed. Although pretreatment of various Toll-like receptor (TLR) ligands have already been reported to be effective in the defense against subsequent IAV infection, the efficacy was limited to specific subtypes, and safety concerns were also raised. In this study, we investigated the protective effect of an attenuated bacterial outer membrane vesicle ­harboring modified lipid A moiety of lipopolysaccharide (fmOMV) against IAV infection and the underlying mechanisms. Administration of fmOMV conferred significant protection against a lethal dose of pandemic H1N1, PR8, H5N2, and highly pathogenic H5N1 viruses; this broad antiviral activity was dependent on macrophages but independent of neutrophils. fmOMV induced recruitment and activation of macrophages and elicited type I IFNs. Intriguingly, fmOMV showed a more significant protective effect than other TLR ligands tested in previous reports, without exhibiting any adverse effect. These results show the potential of fmOMV as a prophylactic agent for the defense against influenza virus infection.</p>
</abstract>
<kwd-group>
<title>Key Words</title>
<kwd>Influenza</kwd>
<kwd>Outer membrane vesicle</kwd>
<kwd>Antiviral</kwd>
<kwd>Macrophages</kwd>
<kwd>Type I interferon</kwd>
</kwd-group>
<counts>
<fig-count count="5"></fig-count>
<ref-count count="49"></ref-count>
<page-count count="14"></page-count>
</counts>
</article-meta>
</front>
</pmc>
</record>

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