Changes in Cytokine Levels and NK Cell Activation Associated with Influenza

Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza virus, are poorly documented. Here, we examined changes in NK cell phenotype and function and plasma cytokine levels associated with influenza infection and vaccination. We show that absolute numbers of peripheral blood NK cells, and particularly those of CD56bright NK cells, decreased upon acute influenza infection while this NK cell subset expanded following intramuscular influenza vaccination. NK cells exposed to influenza antigens were activated, with higher proportions of NK cells expressing CD69 in study subjects infected with seasonal influenza strains. Vaccination led to increased levels of CD25+ NK cells, and notably CD56bright CD25+ NK cells, whereas decreased amounts of this subset were present in the peripheral blood of influenza infected individuals, and predominantly in study subjects infected with the 2009 pandemic H1N1 influenza virus. Finally, acute influenza infection was associated with low plasma concentrations of inflammatory cytokines, including IFN-γ, MIP-1β, IL-2 and IL-15, and high levels of the anti-inflammatory cytokines IL-10 and IL-1ra. Altogether, these data suggest a role for the CD56bright NK cell subset in the response to influenza, potentially involving their recruitment to infected tissues and a local production and/or uptake of inflammatory cytokines

NK cells control HIV‐1 infection of macrophages through soluble factors and cellular contacts in the human decidua

International audienceBackground: During the first trimester of pregnancy, HIV‑1 in utero transmission is rare despite the permissivity of the placenta and the decidua (the uterine mucosa during pregnancy) to infection. In the decidua from the first trimester of pregnancy, macrophages (dMs) are the HIV‑1 main target cells. Decidual natural killer (dNK) cells account for 70 % of decidual leukocytes. They display distinct phenotype and functions compared to peripheral NK cells. At the periphery, NK cells are involved in the control of HIV‑1 infection. In this study, we investigate whether human decidual natural killer (dNK) cells control dM HIV‑1 infection. Results: Autologous cocultures of infected dMs with dNK cells reveal that dNK cells strongly inhibit dM HIV‑1 infec‑ tion. The addition of dNK cells to dMs at different times after infection suggests that the control occurs before the complete establishment of the infection. Double chamber cocultures show that cellular contacts are necessary for an optimal control of infection. Nevertheless, soluble factors secreted by dMs and dNK cells in double chamber cocul‑ tures partially inhibit dM HIV‑1 infection, indicating that soluble factors have also a role in the control of infection. IFN‑γ secretion is increased in infected and uninfected cocultures. We show that IFN‑γ is involved in the control of dM HIV‑1 infection by dNK cells.Conclusions: These results demonstrate that human dNK cells inhibit efficiently HIV‑1 infection in dMs in vitro, and highlight the role of innate immune determinants in the control of HIV‑1 transmission

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Additional file 3: Figure S3. CCL4 and CCL5 concentrations in the culture supernatants. CCL4 and CCL5 concentrations in 48h supernatants of infected dMs, infected double chamber cocultures, infected cocultures and dNK cells are depicted on the graph in pg/mL (9 donors, except for dNK cell supernatants, 6 donors). The medians are displayed. The sign-rank test for paired data was used. * p=0.031; ** p=0.004

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Additional file 4: Figure S4. Purity of dM and dNK cells. The purity of dNK cells (CD14- CD56+) and dMs (CD14+ CD56-) was checked by flow cytometry after cell isolation. A representative example is shown