Natural killer cell-derived IL-10 regulates T cell response to prevent liver damage during sustained murine cytomegalovirus infection
Lee, Alaa Kassim Ali, Amandeep Kaur Komal, Saeedah Musaed Almutairi, and Seung-Hwan . 2019
Natural Killer (NK) cells are lymphocytes of the innate immune response that play a vital role in controlling infections and cancer. Their pro-inflammatory role has been well-established; however, less is known about the regulatory functions of NK cells, in particular, their production of the anti-inflammatory cytokine IL-10. In this study, we investigated the immunoregulatory function of NK cells during MCMV infection and demonstrated that NK cells are major producers of IL-10 during the early stage of infection. To investigate the effect of NK cell-derived IL-10, we have generated NK cell-specific IL-10-deficient mice (NKp46-Cre-Il10 fl/fl ) displaying no signs of age-related spontaneous inflammation, with NK cells that show no detectable IL-10 production upon in vitro stimulation. In NKp46-Cre-Il10 fl/fl mice, the levels of IL-10 and IFNγ, viral burdens and T cell activation were similar between NKp46-Cre-Il10 fl/fl mice and their control littermates, suggesting that NK cell-derived IL-10 is dispensable during acute MCMV infection in immunocompetent hosts. In perforin-deficient mice that show a more sustained infection, NK cells produce more sustained levels of IL-10. By crossing NKp46-Cre-Il10 fl/flmice with perforin-deficient mice, we demonstrated that NK cell-derived IL-10 regulates T cell activation, prevents liver damage, and allows for better disease outcome. Taken together, NK cell-derived IL-10 can be critical in regulating the immune response during early phases of infection and therefore protecting the host from excessive immunopathology.
Upon inflammation, natural killer (NK) cells undergo metabolic changes to support their high energy demand for effector function and proliferation. The metabolic changes are usually accompanied by…
Natural Killer (NK) cells are lymphocytes of the innate immune response that play a vital role in controlling infections and cancer. Their pro-inflammatory role has been well-established; however…