Related Experiment Videos
Increased susceptibility of mice to MHV 3 infection induced by hypercholesterolemic diet: impairment of Kupffer cell
Abstract:
Nutritionally induced hypercholesterolemia in A/J mice causes susceptibility to Mouse Hepatitis type 3 (MHV 3), whereas normal A/J mice are fully resistant. A/J mice fed with a hypercholesterolemic diet for 15 to 60 days develop 5 to 7 days after MHV 3 infection an acute hepatitis which led to high levels of mortality. A direct relationship was found between the high levels of plasma and hepatic cholesterol and the mortality. In attempting to define the dietary-induced physiological changes which led to the loss of resistance, the Kupffer cells were shown to exhibit an impairment of functions in their ability to become activated by LPS in order to take up C3-coated IgM opsonized sheep red blood cells, C3(IgM)SRBC, or 3H-thymidine Escherichia coli, and the susceptibility to interferon (IFN) for the induction of an antiviral state. Peritoneal macrophages which were studied in comparison with the Kupffer cells showed no impaired functions. The findings presented here indicate an inhibition of host resistance, by nutritional hypercholesterolemia, of A/J mice to MHV 3 infection and that, at least one site of impairment occurs specifically at the stage of Kupffer cells function.
Insights
Nutritional hypercholesterolemia impairs Kupffer cell function in A/J mice, increasing susceptibility to Mouse Hepatitis type 3 (MHV-3) infection and mortality. This study identifies Kupffer cell dysfunction as a key factor in diet-induced susceptibility to viral hepatitis.
Area of Science:
- Immunology
- Hepatology
- Virology
Background:
- Nutritionally induced hypercholesterolemia in A/J mice leads to susceptibility to Mouse Hepatitis type 3 (MHV-3) infection.
- Normal A/J mice are resistant to MHV-3, but hypercholesterolemic mice develop acute hepatitis and high mortality post-infection.
Purpose of the Study:
- To investigate the physiological changes underlying diet-induced susceptibility to MHV-3 in A/J mice.
- To identify specific cellular impairments responsible for the loss of host resistance.
Main Methods:
- A/J mice were fed a hypercholesterolemic diet for 15-60 days.
- Mice were infected with MHV-3, and mortality rates were recorded.
- Kupffer cell and peritoneal macrophage functions were assessed, including activation by LPS and uptake of C3-coated sheep red blood cells and E. coli.
- Susceptibility to interferon (IFN) for antiviral state induction was evaluated.
Main Results:
- A direct correlation was observed between high plasma/hepatic cholesterol levels and mortality.
- Kupffer cells from hypercholesterolemic mice showed impaired function, including reduced ability to phagocytose C3-coated sheep red blood cells and E. coli.
- Kupffer cells also exhibited impaired induction of an antiviral state by interferon.
- Peritoneal macrophages did not show impaired functions, indicating Kupffer cell specificity.
Conclusions:
- Nutritional hypercholesterolemia inhibits host resistance to MHV-3 in A/J mice.
- Impaired Kupffer cell function is a critical factor in this diet-induced susceptibility to MHV-3 infection.