Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses
Identifieur interne : 001A45 ( Ncbi/Curation ); précédent : 001A44; suivant : 001A46Oseltamivir 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.
Descripteurs français
- KwdFr :
- Adolescent, Adulte, Animaux, Antiviraux (usage thérapeutique), Charge virale (), Enfant, Enfant d'âge préscolaire, Femelle, Furets, Grippe humaine (), Grippe humaine (immunologie), Grippe humaine (virologie), Humains, Infections à Orthomyxoviridae (), Infections à Orthomyxoviridae (immunologie), Infections à Orthomyxoviridae (virologie), Inflammation (), Inflammation (immunologie), Inflammation (virologie), Jeune adulte, Lymphocytes T CD4+ (), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD4+ (virologie), Lymphocytes T CD8+ (), Lymphocytes T CD8+ (immunologie), Lymphocytes T CD8+ (virologie), Mâle, Nourrisson, Oséltamivir (usage thérapeutique), Souris, Souris de lignée C57BL, Sous-type H1N1 du virus de la grippe A (), Sous-type H1N1 du virus de la grippe A (immunologie).
- MESH :
- immunologie : Grippe humaine, Infections à Orthomyxoviridae, Inflammation, Lymphocytes T CD4+, Lymphocytes T CD8+, Sous-type H1N1 du virus de la grippe A.
- usage thérapeutique : Antiviraux, Oséltamivir.
- virologie : Grippe humaine, Infections à Orthomyxoviridae, Inflammation, Lymphocytes T CD4+, Lymphocytes T CD8+.
- Adolescent, Adulte, Animaux, Charge virale, Enfant, Enfant d'âge préscolaire, Femelle, Furets, Grippe humaine, Humains, Infections à Orthomyxoviridae, Inflammation, Jeune adulte, Lymphocytes T CD4+, Lymphocytes T CD8+, Mâle, Nourrisson, Souris, Souris de lignée C57BL, Sous-type H1N1 du virus de la grippe A.
English descriptors
- KwdEn :
- Adolescent, Adult, Animals, Antiviral Agents (therapeutic use), CD4-Positive T-Lymphocytes (drug effects), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (virology), CD8-Positive T-Lymphocytes (drug effects), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (virology), Child, Child, Preschool, Female, Ferrets, Humans, Infant, Inflammation (immunology), Inflammation (prevention & control), Inflammation (virology), Influenza A Virus, H1N1 Subtype (drug effects), Influenza A Virus, H1N1 Subtype (immunology), Influenza, Human (immunology), Influenza, Human (prevention & control), Influenza, Human (virology), Male, Mice, Mice, Inbred C57BL, Orthomyxoviridae Infections (immunology), Orthomyxoviridae Infections (prevention & control), Orthomyxoviridae Infections (virology), Oseltamivir (therapeutic use), Viral Load (drug effects), Young Adult.
- MESH :
- chemical , therapeutic use : Antiviral Agents, Oseltamivir.
- drug effects : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Influenza A Virus, H1N1 Subtype, Viral Load.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Inflammation, Influenza A Virus, H1N1 Subtype, Influenza, Human, Orthomyxoviridae Infections.
- prevention & control : Inflammation, Influenza, Human, Orthomyxoviridae Infections.
- virology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Inflammation, Influenza, Human, Orthomyxoviridae Infections.
- Adolescent, Adult, Animals, Child, Child, Preschool, Female, Ferrets, Humans, Infant, Male, Mice, Mice, Inbred C57BL, Young Adult.
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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PMC:4473273Le document en format XML
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<country xml:lang="fr">Australie</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Oseltamivir Prophylaxis Reduces Inflammation and Facilitates Establishment of Cross-Strain Protective T Cell Memory to Influenza Viruses</title>
<author><name sortKey="Bird, Nicola L" sort="Bird, Nicola L" uniqKey="Bird N" first="Nicola L." last="Bird">Nicola L. Bird</name>
<affiliation wicri:level="4"><nlm:aff id="aff001"><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>
</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>
<orgName type="university">Université de Melbourne</orgName>
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<author><name sortKey="Olson, Matthew R" sort="Olson, Matthew R" uniqKey="Olson M" first="Matthew R." last="Olson">Matthew R. Olson</name>
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</nlm:aff>
<country xml:lang="fr">Australie</country>
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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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</nlm:aff>
<country xml:lang="fr">Australie</country>
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</nlm:aff>
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<author><name sortKey="Oshansky, Christine M" sort="Oshansky, Christine M" uniqKey="Oshansky C" first="Christine M." last="Oshansky">Christine M. Oshansky</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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</placeName>
</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>
<wicri:regionArea>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</wicri:regionArea>
<wicri:noRegion>Parkville VIC 3010</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Chua, Brendon Y" sort="Chua, Brendon Y" uniqKey="Chua B" first="Brendon Y." last="Chua">Brendon Y. Chua</name>
<affiliation wicri:level="4"><nlm:aff id="aff001"><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>
</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>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sun, Yilun" sort="Sun, Yilun" uniqKey="Sun Y" first="Yilun" last="Sun">Yilun Sun</name>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN 38105, United States of America</addr-line>
</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>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tang, Li" sort="Tang, Li" uniqKey="Tang L" first="Li" last="Tang">Li Tang</name>
<affiliation wicri:level="2"><nlm:aff id="aff005"><addr-line>Department of Biostatistics, St Jude Children’s Research Hospital, Memphis, TN 38105, United States of America</addr-line>
</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>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Handel, Andreas" sort="Handel, Andreas" uniqKey="Handel A" first="Andreas" last="Handel">Andreas Handel</name>
<affiliation wicri:level="2"><nlm:aff id="aff006"><addr-line>Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, University of Georgia, Athens, GA 30602</wicri:regionArea>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jackson, David C" sort="Jackson, David C" uniqKey="Jackson D" first="David C." last="Jackson">David C. Jackson</name>
<affiliation wicri:level="4"><nlm:aff id="aff001"><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>
</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>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Turner, Stephen J" sort="Turner, Stephen J" uniqKey="Turner S" first="Stephen J." last="Turner">Stephen J. Turner</name>
<affiliation wicri:level="4"><nlm:aff id="aff001"><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>
</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>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Thomas, Paul G" sort="Thomas, Paul G" uniqKey="Thomas P" first="Paul G." last="Thomas">Paul G. Thomas</name>
<affiliation wicri:level="2"><nlm:aff id="aff004"><addr-line>Department of Immunology, St Jude Children’s Research Hospital, Memphis, TN 38105, United States of America</addr-line>
</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Immunology, St Jude Children’s Research Hospital, Memphis, TN 38105</wicri:regionArea>
<placeName><region type="state">Tennessee</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kedzierska, Katherine" sort="Kedzierska, Katherine" uniqKey="Kedzierska K" first="Katherine" last="Kedzierska">Katherine Kedzierska</name>
<affiliation wicri:level="4"><nlm:aff id="aff001"><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>
</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>
<orgName type="university">Université de Melbourne</orgName>
<placeName><settlement type="city">Melbourne</settlement>
<region type="état">Victoria (État)</region>
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<series><title level="j">PLoS ONE</title>
<idno type="eISSN">1932-6203</idno>
<imprint><date when="2015">2015</date>
</imprint>
</series>
</biblStruct>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Antiviral Agents (therapeutic use)</term>
<term>CD4-Positive T-Lymphocytes (drug effects)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (virology)</term>
<term>CD8-Positive T-Lymphocytes (drug effects)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (virology)</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Female</term>
<term>Ferrets</term>
<term>Humans</term>
<term>Infant</term>
<term>Inflammation (immunology)</term>
<term>Inflammation (prevention & control)</term>
<term>Inflammation (virology)</term>
<term>Influenza A Virus, H1N1 Subtype (drug effects)</term>
<term>Influenza A Virus, H1N1 Subtype (immunology)</term>
<term>Influenza, Human (immunology)</term>
<term>Influenza, Human (prevention & control)</term>
<term>Influenza, Human (virology)</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Orthomyxoviridae Infections (immunology)</term>
<term>Orthomyxoviridae Infections (prevention & control)</term>
<term>Orthomyxoviridae Infections (virology)</term>
<term>Oseltamivir (therapeutic use)</term>
<term>Viral Load (drug effects)</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Animaux</term>
<term>Antiviraux (usage thérapeutique)</term>
<term>Charge virale ()</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Femelle</term>
<term>Furets</term>
<term>Grippe humaine ()</term>
<term>Grippe humaine (immunologie)</term>
<term>Grippe humaine (virologie)</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae ()</term>
<term>Infections à Orthomyxoviridae (immunologie)</term>
<term>Infections à Orthomyxoviridae (virologie)</term>
<term>Inflammation ()</term>
<term>Inflammation (immunologie)</term>
<term>Inflammation (virologie)</term>
<term>Jeune adulte</term>
<term>Lymphocytes T CD4+ ()</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD4+ (virologie)</term>
<term>Lymphocytes T CD8+ ()</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T CD8+ (virologie)</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Oséltamivir (usage thérapeutique)</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Sous-type H1N1 du virus de la grippe A ()</term>
<term>Sous-type H1N1 du virus de la grippe A (immunologie)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="therapeutic use" xml:lang="en"><term>Antiviral Agents</term>
<term>Oseltamivir</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Viral Load</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Grippe humaine</term>
<term>Infections à Orthomyxoviridae</term>
<term>Inflammation</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>Inflammation</term>
<term>Influenza A Virus, H1N1 Subtype</term>
<term>Influenza, Human</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="prevention & control" xml:lang="en"><term>Inflammation</term>
<term>Influenza, Human</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" qualifier="usage thérapeutique" xml:lang="fr"><term>Antiviraux</term>
<term>Oséltamivir</term>
</keywords>
<keywords scheme="MESH" qualifier="virologie" xml:lang="fr"><term>Grippe humaine</term>
<term>Infections à Orthomyxoviridae</term>
<term>Inflammation</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
</keywords>
<keywords scheme="MESH" qualifier="virology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>Inflammation</term>
<term>Influenza, Human</term>
<term>Orthomyxoviridae Infections</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adolescent</term>
<term>Adult</term>
<term>Animals</term>
<term>Child</term>
<term>Child, Preschool</term>
<term>Female</term>
<term>Ferrets</term>
<term>Humans</term>
<term>Infant</term>
<term>Male</term>
<term>Mice</term>
<term>Mice, Inbred C57BL</term>
<term>Young Adult</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adolescent</term>
<term>Adulte</term>
<term>Animaux</term>
<term>Charge virale</term>
<term>Enfant</term>
<term>Enfant d'âge préscolaire</term>
<term>Femelle</term>
<term>Furets</term>
<term>Grippe humaine</term>
<term>Humains</term>
<term>Infections à Orthomyxoviridae</term>
<term>Inflammation</term>
<term>Jeune adulte</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Mâle</term>
<term>Nourrisson</term>
<term>Souris</term>
<term>Souris de lignée C57BL</term>
<term>Sous-type H1N1 du virus de la grippe A</term>
</keywords>
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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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