Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice
Abstract Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-04-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-58931-y |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850181928670461952 |
|---|---|
| author | Anna Schmidt Jana Fuchs Mark Dedden Katharina Kocher Christine Schülein Julian Hübner Ana Vieira Antão Pascal Irrgang Friederike Oltmanns Vera Viherlehto Natascha Leicht Ralf Joachim Rieker Carol Geppert Uwe Appelt Sebastian Zundler Kilian Schober Dennis Lapuente Matthias Tenbusch |
| author_facet | Anna Schmidt Jana Fuchs Mark Dedden Katharina Kocher Christine Schülein Julian Hübner Ana Vieira Antão Pascal Irrgang Friederike Oltmanns Vera Viherlehto Natascha Leicht Ralf Joachim Rieker Carol Geppert Uwe Appelt Sebastian Zundler Kilian Schober Dennis Lapuente Matthias Tenbusch |
| author_sort | Anna Schmidt |
| collection | DOAJ |
| description | Abstract Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8+ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines. |
| format | Article |
| id | doaj-art-e2c4e0b9519f4bb8b252b5a2d2d30fe0 |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-e2c4e0b9519f4bb8b252b5a2d2d30fe02025-08-20T02:17:48ZengNature PortfolioNature Communications2041-17232025-04-0116111810.1038/s41467-025-58931-yInflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in miceAnna Schmidt0Jana Fuchs1Mark Dedden2Katharina Kocher3Christine Schülein4Julian Hübner5Ana Vieira Antão6Pascal Irrgang7Friederike Oltmanns8Vera Viherlehto9Natascha Leicht10Ralf Joachim Rieker11Carol Geppert12Uwe Appelt13Sebastian Zundler14Kilian Schober15Dennis Lapuente16Matthias Tenbusch17Friedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyDepartment of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergMikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-NürnbergMikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-NürnbergFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyInstitute of Pathology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergInstitute of Pathology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergInstitute of Pathology, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergIZKF, Nikolaus-Fiebiger-Centre of Molecular Medicine, Friedrich-Alexander-Universität Erlangen-NürnbergDepartment of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-NürnbergMikrobiologisches Institut – Klinische Mikrobiologie, Immunologie und Hygiene, Universitätsklinikum Erlangen und Friedrich-Alexander-Universität Erlangen-NürnbergFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyFriedrich-Alexander-Universität Erlangen-Nürnberg, University Hospital Erlangen, Institute of Clinical and Molecular VirologyAbstract Lung tissue-resident memory T cells (TRM) are critical for the local control of respiratory tract infections caused by influenza A viruses (IAV). Here we compare TRM populations induced by intranasal adenoviral vector vaccines encoding hemagglutinin and nucleoprotein (NP) with those induced by an H1N1 infection in BALB/c mice. While vaccine-induced TRM express high levels of CD103 and persist longer in the lung parenchyma, short-lived, H1N1-induced TRM have a transcriptome associated with higher cytotoxic potential and distinct transcriptional profile as shown by single-cell RNA sequencing. In both the vaccine and H1N1 groups, NP-specific CD8+ T cells expand during heterologous influenza virus infection and protect the mice from disease. Meanwhile, lung inflammation in response to an infection with unrelated respiratory syncytial virus do not influence the fate of pre-existing TRM. Our preclinical work thus confirms that inflammatory conditions in the tissue shape the phenotypic and functional characteristics of TRM to serve relevant informations for optimizing mucosal vaccines.https://doi.org/10.1038/s41467-025-58931-y |
| spellingShingle | Anna Schmidt Jana Fuchs Mark Dedden Katharina Kocher Christine Schülein Julian Hübner Ana Vieira Antão Pascal Irrgang Friederike Oltmanns Vera Viherlehto Natascha Leicht Ralf Joachim Rieker Carol Geppert Uwe Appelt Sebastian Zundler Kilian Schober Dennis Lapuente Matthias Tenbusch Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice Nature Communications |
| title | Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice |
| title_full | Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice |
| title_fullStr | Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice |
| title_full_unstemmed | Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice |
| title_short | Inflammatory conditions shape phenotypic and functional characteristics of lung-resident memory T cells in mice |
| title_sort | inflammatory conditions shape phenotypic and functional characteristics of lung resident memory t cells in mice |
| url | https://doi.org/10.1038/s41467-025-58931-y |
| work_keys_str_mv | AT annaschmidt inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT janafuchs inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT markdedden inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT katharinakocher inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT christineschulein inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT julianhubner inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT anavieiraantao inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT pascalirrgang inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT friederikeoltmanns inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT veraviherlehto inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT nataschaleicht inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT ralfjoachimrieker inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT carolgeppert inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT uweappelt inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT sebastianzundler inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT kilianschober inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT dennislapuente inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice AT matthiastenbusch inflammatoryconditionsshapephenotypicandfunctionalcharacteristicsoflungresidentmemorytcellsinmice |