Fig. 3

Immune response to CMV infection in the liver. A Innate immune response in the liver. Kupffer cells produce type I interferon (IFNαβ) in response to infection, stimulating the production of MCP-1. MCP-1 is critical for recruiting inflammatory macrophages that produce MIP-1α to recruit NK cells to sites of infection. NK cells control the virus in the liver in an IFNγ-dependent manner but can also produce TNFα to sustain virus infection. Conventional dendritic cells (cDCs) produce IL-12 to promote IFNγ production by ILC1s. B Adaptive immune response in the liver. CD8 T cells mediate the control of CMV infection in the liver by exhibiting cytotoxic activity. However, the CD8 T cell response to infection in the liver can be exaggerated and can lead to liver pathology. Regulatory T cells (Tregs) and activated NK cells can suppress the pathological response of CD8 T cells to CMV infection in the liver. Tregs (CD4⁺Foxp3⁺ T cells) strongly upregulate the expression of ST-2 receptors and infiltrate the liver in an IL33-dependent manner. IL-33 is produced by F4/80⁺ macrophages. An additional layer of control is exerted by activated NK cells that produce IL-10 and perforin to suppress immunopathology mediated by CD8 T cells in the liver