Natural Killer Cell-Derived IL-10 Prevents Liver Damage During Sustained Murine Cytomegalovirus Infection
FRONTIERS IN IMMUNOLOGY
Authors: Ali, Alaa Kassim; Komal, Amandeep Kaur; Almutairi, Saeedah Musaed; Lee, Seung-Hwan
Abstract
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 IFN gamma, 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/fl) mice 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.
Effect of the total replacement of fishmeal with plant proteins and supplemental essential amino acids in the extruded diet on antioxidants genes, enzyme activities, and immune response in juvenile blunt snout bream
AQUACULTURE INTERNATIONAL
Authors: Mokrani, Ahmed; Ren, Mingchun; Liang, Hualiang; Yang, Qiang; Ji, Ke; Kasiya, Hopeson Chisomo; Ge, Xianping
Abstract
Four diets were formulated with or without fishmeal (FM) and essential amino acid (EAA) supplementation fed to the blunt snout bream throughout 8 weeks. The results showed that total cholesterol level (TC) was decreased significantly against FM reduction (P < 0.05). Aspartate aminotransferase (AST), alanine transaminases (ALT), and alkaline phosphatase (ALP) activities were affected neither by FM reduction nor EAA supplementation (P > 0.05). Catalase (CAT) activity and glutathione (GSH) content were significantly augmented and diminished in the group fed diet 3 respectively (P < 0.05). Superoxide dismutase (SOD) activity and malondialdehyde (MDA) content did not alter either by FM reduction or EAA supplementation (P > 0.05). Glutathione peroxidase (GPx) activity was elevated significantly either by reducing FM or supplementing EAA (P < 0.05). The relative expression of nuclear factor erythroid 2-related factor 2 (Nrf2), Kelch-like-ECH-associated protein 1 (Keap1), and GPx was significantly augmented (P < 0.05) in the EAA-supplemented groups. Neither FM reduction nor EAA supplementation altered the relative expression of SOD (P > 0.05), whereas the relative expression of copper-zinc superoxide dismutase (Cu/Zn-SOD) decreased against FM reduction (P < 0.05). The relative expressions of Interleukin 8 (IL-8), tumour necrosis factor-alpha (TNF-alpha), interleukin 10 (IL10), and nuclear factor-kappa B (NF-kappa B) were diminished significantly in FM-reduced groups (P < 0.05). The supplementation of EAA significantly increased the relative expression of signal transducer and activator of transcription 4 (STAT4) (P < 0.05). In conclusion, the results revealed that dietary plant proteins with EAA supplementation significantly affected the physiological status and immune responses in blunt snout bream.