Increased susceptibility of mice to MHV 3 infection induced by hypercholesterolemic diet: impairment of Kupffer cell function.

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.