Plasmacytoid Dendritic Cells Contribute to the Protective Immunity Induced by Intranasal Treatment with Fc-fused Interleukin-7 against Lethal Influenza Virus Infection

Abstract

Developing a novel vaccine that can be applied against multiple strains of influenza virus is of utmost importance to human health. Previously, we demonstrated that the intranasal introduction of Fc-fused IL-7 (IL-7-mFc), a long-acting cytokine fusion protein, confers long-lasting prophylaxis against multiple strains of influenza A virus (IAV) by inducing the development of lung-resident memory-like T cells, called TRM-like cells. Here, we further investigated the mechanisms of IL-7-mFc-mediated protective immunity to IAVs. First, we found that IL-7-mFc treatment augments the accumulation of pulmonary T cells in 2 ways: recruiting blood circulating T cells into the lung and expanding T cells at the lung parenchyma. Second, the blockade of T cell migration from the lymph nodes (LNs) with FTY720 treatment was not required for mounting the protective immunity to IAV with IL-7-mFc, suggesting a more important role of IL-7 in T cells in the lungs. Third, IL-7-mFc treatment also recruited various innate immune cells into the lungs. Among these cells, plasmacytoid dendritic cells (pDCs) play an important role in IL-7-mFc-mediated protective immunity through reducing the immunopathology and increasing IAV-specific cytotoxic T lymphocyte (CTL) responses. In summary, our results show that intranasal treatment with IL-7-mFc modulates pulmonary immune responses to IAV, affecting both innate and adaptive immune cells.

Exogenous Interleukin-33 Contributes to Protective Immunity via Cytotoxic T-Cell Priming against Mucosal Influenza Viral Infection

“…For viral titration and cytokine measurements, bronchoalveolar lavage (BAL) fluids from infected mice were collected at the indicated time points by washing with 1 ml of PBS [16].…”

Coronavirus (SARS-CoV-2): a systematic review for potential vaccines

“… 78 In the influenza A virus infection model, it has been described that improved vaccine efficacy shows the accretion of pulmonary T cells and an increase in plasmacytoid dendritic cells by treating with Fc-fused IL-7. 79 Along with the vaccine technologies described here, some other identified hurdles must be overcome to develop a successful vaccine. Antibody-dependent enhancement (ADE) of disease is a phenomenon in which virus-specific antibodies allow the virus to enter into the host cell via the Fc receptor pathway, leading to higher viral infection.…”

The Broad Immunomodulatory Effects of IL-7 and Its Application In Vaccines

“…When mice were intranasally treated with Fc-fused mouse IL-7 (mIL-7-mFc) not native IL-7 protein before lethal influenza A virus (IAV) infection, the percentage of mice that survived was significantly increased (169). In particular, mIL-7-mFc recruited both T cells and pDCs from circulation into the lungs, with T cells transitioning into lung-specific memory-like T cells (T RMlike) and pDCs strengthening lung-specific anti-IAV CTL responses (169,170), thereby providing long-lasting immune responses against lethal AIV infection by altering the pulmonary immune environment. Since IL-7 is locally produced by intestinal epithelial cells, particularly epithelial goblet cells, it can regulate the phenotype and function of intraepithelial lymphocytes (IELs) and lamina propria lymphocytes (LPLs) (171,172).…”