Interferon-λ enhances adaptive mucosal immunity by boosting release of thymic stromal lymphopoietin

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

  • Liang Ye, Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Daniel Schnepf, Spemann Graduate School of Biology and Medicine (SGBM), Albert Ludwigs University Freiburg, Freiburg, Germany.
  • ,
  • Jan Becker, Institute of Virology, Medical Center, University of Freiburg, Freiburg, Germany.
  • ,
  • Karolina Ebert, Institute of Medical Microbiology, Medical Center University of Freiburg, Freiburg, Germany.
  • ,
  • Yakup Tanriver, Department of Internal Medicine IV, Medical Center University of Freiburg, Freiburg, Germany.
  • ,
  • Valentina Bernasconi, Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Sweden;
  • ,
  • Hans Henrik Gad
  • Rune Hartmann
  • Nils Lycke, Department of Oral Microbiology and Immunology, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Sweden;
  • ,
  • Peter Staeheli, Medical Faculty, University of Freiburg, Freiburg, Germany. peter.staeheli@uniklinik-freiburg.de.

Interferon-λ (IFN-λ) acts on mucosal epithelial cells and thereby confers direct antiviral protection. In contrast, the role of IFN-λ in adaptive immunity is far less clear. Here, we report that mice deficient in IFN-λ signaling exhibited impaired CD8+ T cell and antibody responses after infection with a live-attenuated influenza virus. Virus-induced release of IFN-λ triggered the synthesis of thymic stromal lymphopoietin (TSLP) by M cells in the upper airways that, in turn, stimulated migratory dendritic cells and boosted antigen-dependent germinal center reactions in draining lymph nodes. The IFN-λ-TSLP axis also boosted production of the immunoglobulins IgG1 and IgA after intranasal immunization with influenza virus subunit vaccines and improved survival of mice after challenge with virulent influenza viruses. IFN-λ did not influence the efficacy of vaccines applied by subcutaneous or intraperitoneal routes, indicating that IFN-λ plays a vital role in potentiating adaptive immune responses that initiate at mucosal surfaces.

Original languageEnglish
JournalNature Immunology
Volume20
Issue5
Pages (from-to)593-601
Number of pages9
ISSN1529-2908
DOIs
Publication statusPublished - May 2019

    Research areas

  • Adaptive Immunity/drug effects, Animals, Antibody Formation/drug effects, Cells, Cultured, Cytokines/genetics, Dendritic Cells/drug effects, Immunity, Mucosal/drug effects, Immunization/methods, Influenza A virus/drug effects, Influenza Vaccines/administration & dosage, Interleukins/administration & dosage, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Orthomyxoviridae Infections/immunology, Receptors, Interferon/genetics

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