Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses
Identifieur interne : 000A60 ( Pmc/Curation ); précédent : 000A59; suivant : 000A61Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses
Auteurs : Nicola L. Bird [Australie] ; Matthew R. Olson [Australie] ; Aeron C. Hurt [Australie] ; Christine M. Oshansky [États-Unis] ; Ding Yuan Oh [Australie] ; Patrick C. Reading [Australie] ; Brendon Y. Chua [Australie] ; Yilun Sun [États-Unis] ; Li Tang [États-Unis] ; Andreas Handel [États-Unis] ; David C. Jackson [Australie] ; Stephen J. Turner [Australie] ; Paul G. Thomas [États-Unis] ; Katherine Kedzierska [Australie]Source :
- PLoS ONE [ 1932-6203 ] ; 2015.
Abstract
CD8+ T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8+ T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8+ T cell responses and the establishment of immunological CD8+ T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8+ T cell responses. Importantly, functional memory CD8+ T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4+ T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8+ T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves.
Url:
DOI: 10.1371/journal.pone.0129768
PubMed: 26086392
PubMed Central: 4473273
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<author><name sortKey="Hurt, Aeron C" sort="Hurt, Aeron C" uniqKey="Hurt A" first="Aeron C." last="Hurt">Aeron C. Hurt</name>
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<author><name sortKey="Oh, Ding Yuan" sort="Oh, Ding Yuan" uniqKey="Oh D" first="Ding Yuan" last="Oh">Ding Yuan Oh</name>
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</nlm:aff>
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</nlm:aff>
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<author><name sortKey="Reading, Patrick C" sort="Reading, Patrick C" uniqKey="Reading P" first="Patrick C." last="Reading">Patrick C. Reading</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="aff002"><addr-line>WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory (VIDRL), at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010, Australia</addr-line>
</nlm:aff>
<country xml:lang="fr">Australie</country>
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<author><name sortKey="Chua, Brendon Y" sort="Chua, Brendon Y" uniqKey="Chua B" first="Brendon Y." last="Chua">Brendon Y. Chua</name>
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<author><name sortKey="Sun, Yilun" sort="Sun, Yilun" uniqKey="Sun Y" first="Yilun" last="Sun">Yilun Sun</name>
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<author><name sortKey="Tang, Li" sort="Tang, Li" uniqKey="Tang L" first="Li" last="Tang">Li Tang</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN 38105</wicri:regionArea>
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<author><name sortKey="Handel, Andreas" sort="Handel, Andreas" uniqKey="Handel A" first="Andreas" last="Handel">Andreas Handel</name>
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</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602</wicri:regionArea>
</affiliation>
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<author><name sortKey="Jackson, David C" sort="Jackson, David C" uniqKey="Jackson D" first="David C." last="Jackson">David C. Jackson</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
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</affiliation>
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<author><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010</wicri:regionArea>
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<author><name sortKey="Thomas, Paul G" sort="Thomas, Paul G" uniqKey="Thomas P" first="Paul G." last="Thomas">Paul G. Thomas</name>
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<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010</wicri:regionArea>
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<front><div type="abstract" xml:lang="en"><p>CD8<sup>+</sup>
T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8<sup>+</sup>
T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8<sup>+</sup>
T cell responses and the establishment of immunological CD8<sup>+</sup>
T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8<sup>+</sup>
T cell responses. Importantly, functional memory CD8<sup>+</sup>
T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4<sup>+</sup>
T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8<sup>+</sup>
T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves.</p>
</div>
</front>
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<author><name sortKey="Linster, M" uniqKey="Linster M">M Linster</name>
</author>
<author><name sortKey="Chutinimitkul, S" uniqKey="Chutinimitkul S">S Chutinimitkul</name>
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<author><name sortKey="De Wit, E" uniqKey="De Wit E">E de Wit</name>
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</TEI>
<pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id>
<journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id>
<journal-id journal-id-type="publisher-id">plos</journal-id>
<journal-id journal-id-type="pmc">plosone</journal-id>
<journal-title-group><journal-title>PLoS ONE</journal-title>
</journal-title-group>
<issn pub-type="epub">1932-6203</issn>
<publisher><publisher-name>Public Library of Science</publisher-name>
<publisher-loc>San Francisco, CA USA</publisher-loc>
</publisher>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">26086392</article-id>
<article-id pub-id-type="pmc">4473273</article-id>
<article-id pub-id-type="doi">10.1371/journal.pone.0129768</article-id>
<article-id pub-id-type="publisher-id">PONE-D-15-03317</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses</article-title>
<alt-title alt-title-type="running-head">Oseltamivir and CD8<sup>+</sup>
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T Cell Memory</alt-title>
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<xref ref-type="aff" rid="aff001"><sup>1</sup>
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<xref ref-type="aff" rid="aff001"><sup>1</sup>
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</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Reading</surname>
<given-names>Patrick C.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref ref-type="aff" rid="aff002"><sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Chua</surname>
<given-names>Brendon Y.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sun</surname>
<given-names>Yilun</given-names>
</name>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Tang</surname>
<given-names>Li</given-names>
</name>
<xref ref-type="aff" rid="aff005"><sup>5</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Handel</surname>
<given-names>Andreas</given-names>
</name>
<xref ref-type="aff" rid="aff006"><sup>6</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jackson</surname>
<given-names>David C.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Turner</surname>
<given-names>Stephen J.</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thomas</surname>
<given-names>Paul G.</given-names>
</name>
<xref ref-type="aff" rid="aff004"><sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Kedzierska</surname>
<given-names>Katherine</given-names>
</name>
<xref ref-type="aff" rid="aff001"><sup>1</sup>
</xref>
<xref rid="cor001" ref-type="corresp">*</xref>
</contrib>
</contrib-group>
<aff id="aff001"><label>1</label>
<addr-line>Department of Microbiology and Immunology, University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010, Australia</addr-line>
</aff>
<aff id="aff002"><label>2</label>
<addr-line>WHO Collaborating Centre for Reference and Research on Influenza, Victorian Infectious Diseases Reference Laboratory (VIDRL), at the Peter Doherty Institute for Infection and Immunity, Parkville VIC 3010, Australia</addr-line>
</aff>
<aff id="aff003"><label>3</label>
<addr-line>Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria 3010, Australia</addr-line>
</aff>
<aff id="aff004"><label>4</label>
<addr-line>Department of Immunology, St Jude Children’s Research Hospital, Memphis, TN 38105, United States of America</addr-line>
</aff>
<aff id="aff005"><label>5</label>
<addr-line>Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN 38105, United States of America</addr-line>
</aff>
<aff id="aff006"><label>6</label>
<addr-line>Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602, United States of America</addr-line>
</aff>
<aff id="aff007"><label>7</label>
<addr-line>Federation University, School of Applied Sciences and Biomedical Sciences, Gippsland Victoria 3842, Australia</addr-line>
</aff>
<contrib-group><contrib contrib-type="editor"><name><surname>Manicassamy</surname>
<given-names>Balaji</given-names>
</name>
<role>Academic Editor</role>
<xref ref-type="aff" rid="edit1"></xref>
</contrib>
</contrib-group>
<aff id="edit1"><addr-line>The University of Chicago, UNITED STATES</addr-line>
</aff>
<author-notes><fn fn-type="COI-statement" id="coi001"><p><bold>Competing Interests: </bold>
The authors have declared that no competing interests exist.</p>
</fn>
<fn fn-type="con" id="contrib001"><p>Conceived and designed the experiments: KK PGT SJT ACH PCR BC MRO DJ. Performed the experiments: NB CMO DYO MRO KK BC. Analyzed the data: NB ACH CMO DYO MRO YS LT AH PGT. Contributed reagents/materials/analysis tools: YS LT AH PGT ACH. Wrote the paper: NB ACH CMO DYO PCR MRO YS LT AH SJT PGT KK DJ.</p>
</fn>
<fn fn-type="current-aff" id="currentaff001"><label>¤</label>
<p>Current address: Department of Pediatrics, Herman B. Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, United States of America</p>
</fn>
<corresp id="cor001">* E-mail: <email>kkedz@unimelb.edu.au</email>
</corresp>
</author-notes>
<pub-date pub-type="epub"><day>18</day>
<month>6</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="collection"><year>2015</year>
</pub-date>
<volume>10</volume>
<issue>6</issue>
<elocation-id>e0129768</elocation-id>
<history><date date-type="received"><day>19</day>
<month>3</month>
<year>2015</year>
</date>
<date date-type="accepted"><day>24</day>
<month>4</month>
<year>2015</year>
</date>
</history>
<permissions><copyright-statement>© 2015 Bird et al</copyright-statement>
<copyright-year>2015</copyright-year>
<copyright-holder>Bird et al</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.</license-p>
</license>
</permissions>
<self-uri content-type="pdf" xlink:type="simple" xlink:href="pone.0129768.pdf"></self-uri>
<abstract><p>CD8<sup>+</sup>
T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8<sup>+</sup>
T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8<sup>+</sup>
T cell responses and the establishment of immunological CD8<sup>+</sup>
T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8<sup>+</sup>
T cell responses. Importantly, functional memory CD8<sup>+</sup>
T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4<sup>+</sup>
T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8<sup>+</sup>
T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves.</p>
</abstract>
<funding-group><funding-statement>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The work was supported by Australian National Health and Medical Research Council (NHMRC) Project Grant to KK (GNT1008854), NHMRC Program Grant to SJT (GNT567122), a CASS Foundation Project Grant (to KK), and US government funds through the National Institute of Allergy and Infectious Diseases, the National Institutes of Health, under contract numbers HHSN266200700005C and HHSN272201400006C (Centers of Excellence for Influenza Research and Surveillance) to PT and ALSAC to PT. KK is a NHMRC Career Development Fellow Level 2 and SJT is an ARC Future Fellow Level 3. The Melbourne WHO Collaborating Centre for Reference and Research on Influenza is supported by the Australian Government Department of Health.</funding-statement>
</funding-group>
<counts><fig-count count="9"></fig-count>
<table-count count="1"></table-count>
<page-count count="21"></page-count>
</counts>
<custom-meta-group><custom-meta id="data-availability"><meta-name>Data Availability</meta-name>
<meta-value>All relevant data are within the paper and its Supporting Information files.</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
<notes><title>Data Availability</title>
<p>All relevant data are within the paper and its Supporting Information files.</p>
</notes>
</front>
</pmc>
</record>
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