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

Nat Immunol. 2019 May;20(5):593-601. doi: 10.1038/s41590-019-0345-x. Epub 2019 Mar 18.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Cytokines
  • IFNLR1 protein, mouse
  • IL28A protein, mouse
  • Influenza Vaccines
  • Interleukins
  • Receptors, Interferon
  • thymic stromal lymphopoietin