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.
| Original language | English |
|---|---|
| Journal | Nature Immunology |
| Volume | 20 |
| Issue | 5 |
| Pages (from-to) | 593-601 |
| Number of pages | 9 |
| ISSN | 1529-2908 |
| DOIs | |
| Publication status | Published - May 2019 |
Keywords
- 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