Per- and poly-fluoroalkyl substances exposure dysregulate immune responses and exacerbate liver injury in viral hepatitis

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B1008
Abstract ID: 5299

Presenting Author:
Hui Wang , Instructor at Univ. of Texas Med. Br., Galveston

Abstract:

Per- and poly-fluoroalkyl substances (PFAS), ubiquitous environmental contaminants and known as "forever chemicals," are commonly found in drinking water supplies worldwide and have increasingly been associated with various adverse health effects. Emerging evidence suggests an association of PFAS exposure with immune dysregulation and inflammatory disorders. However, the impact and underlying mechanisms of PFAS in immune dysregulation and viral infections remain unclear. To explore this, we first administered perfluorooctanoic acid (PFOA) to C57BL/6 mice via gavage at doses of 2.5 and 7.5 mg/kg/day for two weeks and examined the immune cell responses in the spleen. PFOA exposure led to significant decreases in various splenic immune cells, including T cells, NK cells, B cells and dendritic cells. Additionally, PFOA exposure induced liver toxicity, as evident from elevated serum alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels. Secondly, using a mouse model infected with lymphocytic choriomeningitis virus, we observed that PFOA exposure impaired multi-functional T cell responses, evidenced by substantial reductions in cytokine-producing CD4 and CD8 T cells. Furthermore, increased serum ALT and ALP levels following PFOA treatment suggested exacerbation of liver injury. Our studies provide evidence that PFAS exposure causes immune dysregulation, hampers antiviral immunity and aggravates liver injury in viral hepatitis.