Abstract
Various cell types in both lymphoid and non-lymphoid tissues produce the anti-inflammatory cytokine interleukin (IL)-10 during murine cytomegalovirus (MCMV) infection. The functions of IL-10 in the liver during acute infection and the cells that generate this cytokine at this site have not been extensively investigated. In this study, we demonstrate that the production of IL-10 in the liver is elevated in C57BL/6 mice during late acute MCMV infection. Using IL-10 green fluorescence protein (GFP) reporter knock-in mice, designated IL-10-internal ribosomal entry site (IRES)-GFP-enhanced reporter (tiger), NK cells are identified as major IL-10 expressing cells in the liver after infection, along with T cells and other leukocytes. In the absence of IL-10, mice exhibit marked elevations in proinflammatory cytokines and in the numbers of mononuclear cells and lymphocytes infiltrating the liver during this infection. IL-10-deficiency also enhances liver injury without improving viral clearance from this site. Collectively, the results indicate that IL-10-producing cells in the liver provide protection from collateral injury by modulating the inflammatory response associated with MCMV infection.
Highlights
An effective immune response against microbial pathogens is dictated by a fine equilibrium between host defense and inflammatory tissue damage
Because the rise in IL-10 protein levels coincided with a period of NK cell expansion [34,35] and T cell recruitment [23,24,25,26,36] in the livers of MCMV-infected mice, we evaluated the relative contributions of NK cells and T cells to liver IL-10 expression
To identify the cells expressing IL-10 on day 4 after MCMV infection, liver leukocytes were prepared from IL-10-(IRES)-green fluorescence protein (GFP)-enhanced reporter mice infected for 4 days
Summary
An effective immune response against microbial pathogens is dictated by a fine equilibrium between host defense and inflammatory tissue damage. While enhanced immune responses and viral eradication achieved in the absence of IL-10 may be desirable outcomes, the absence of IL-10 may promote unwanted immune mediated pathology with or without improved viral elimination depending on the site of infection [12,13,14,15,16]. In these occasions, IL-10 may be necessary to reduce collateral damage due to inflammatory antiviral responses. These varied outcomes imply the central role of IL-10 in regulating the magnitude of immune responses, and underscore the necessity for detailed studies of how IL-10 regulates immunity to infection for the benefit or detriment of the host
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