Examining the immune response to infection in the context of Non-alcoholic fatty liver disease (NAFLD)
Date
2022-02
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NAFLD includes a spectrum of disease from minor steatosis to hepatic inflammation, and can develop into fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Due to the obesity epidemic, NAFLD is rapidly emerging as the most common chronic liver disease worldwide. Although the exact pathogenic progression of NAFLD is ambiguous, the evolution from steatosis to NAFLD is currently considered a multi-hit approach involving inflammation that may promote progression of the disease, although there is very little data regarding immune response to pathogens in the context of NAFLD. The hypothesis states the immune response to viral infection in the context of fatty liver is hyperinflammatory, resulting in accelerated and increased liver damage. Intravital microscopy (IVM) is a sophisticated imaging approach that allows us to see cellular interactions and behaviours in real-time in vivo. IVM of the fatty liver revealed anatomical changes to the liver after high fat diet (HFD) and a pro-inflammatory resident macrophage phenotype. After infection with S. aureus, HFD mice had decreased platelets and NETs in the liver, while plasma IL-17 was increased compared to control. However, NAFLD mice showed similar bacterial loads and alanine aminotransferase (ALT) levels compared to control. Infection with adenovirus resulted in a delayed GFP expression but increased liver damage as assessed by ALTs. Importantly, flow cytometric analysis showed exhausted T cells from NAFLD mice that did not activate as well as control T cells after stimulation, while IVM revealed no behavioural dysfunction of T cells from NAFLD mice post-viral infection. Overall, these results reveal small but important alterations in the immune response to both bacterial and viral infection in the context of NAFLD.
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Davis, R. (2022). Examining the immune response to infection in the context of Non-alcoholic fatty liver disease (NAFLD) (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.