Journal Article

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

Tanriver, Yakup, Bernasconi, Valentina, Ye, Liang, Ebert, Karolina, Lycke, Nils, Becker, Jan, Staeheli, Peter, Gad, Hans Henrik, Hartmann, Rune, Schnepf, Daniel

2019

Overview

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. The role of IFN-λ in adaptive immunity is not well characterized. Staeheli and colleagues show that in the lungs, IFN-λ elicits production of the cytokine TSLP from M cells and that this in turn is essential for effective adaptive immunity and control of infection with influenza virus.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/250 / 631/250/127 / 631/250/2152 / 631/250/254 / 631/250/347 / Adaptive immunity / Adaptive Immunity - drug effects / Adaptive Immunity - genetics / Adaptive Immunity - immunology / Animals / Antibody Formation - drug effects / Antibody Formation - immunology / Biomedical and Life Sciences / Biomedicine / CD8 antigen / Cell migration / Cells, Cultured / Cytokines - genetics / Cytokines - immunology / Cytokines - metabolism / Dendritic cells / Dendritic Cells - drug effects / Dendritic Cells - immunology / Dendritic Cells - virology / Epithelial cells / Immunity, Mucosal - drug effects / Immunity, Mucosal - genetics / Immunity, Mucosal - immunology / Immunization / Immunization - methods / Immunoglobulin A / Immunoglobulin G / Immunologi inom det medicinska området / Immunology / Immunology in the Medical Area / Infectious Diseases / Influenza / Influenza A virus - drug effects / Influenza A virus - immunology / Influenza A virus - physiology / Influenza Vaccines - administration & dosage / Influenza Vaccines - immunology / Interferon / Interleukins - administration & dosage / Interleukins - immunology / Lymph nodes / Lymphocytes T / M cells / Mice, Inbred BALB C / Mice, Inbred C57BL / Mice, Inbred DBA / Mice, Knockout / Mucosal immunity / Orthomyxoviridae Infections - immunology / Orthomyxoviridae Infections - prevention & control / Orthomyxoviridae Infections - virology / Receptors, Interferon - genetics / Receptors, Interferon - immunology / Receptors, Interferon - metabolism / Thymic stromal lymphopoietin / Thymus / Vaccines / Viruses