Dietary Cholesterol Affects The Pathogenesis Of Influenza A Virus Infection In Mice

Abstract Influenza is one of the most prevalent and devastating infectious diseases in the world. But it is unclear how host factors may function to increase disease susceptibility or severity. Here, we sought to determine the role of dietary cholesterol in modulating the immune response or altering viral activity during influenza A infection. A pilot experiment indicated mice fed a 2% cholesterol diet prior to inoculation with mouse-adapted human influenza A virus (Puerto Rico/8/1934 H1N1; 1 HAU) exhibit greater morbidity compared to controls fed an energy density-matched diet. To confirm these data, 5-week-old C57BL/6 mice were fed either standard rodent diet or matched diet with 2% cholesterol for 5 weeks, then inoculated intranasally with either saline or flu (0.7 HAU). The effect of diet on circulating leukocytes was determined by flow cytometry. Serum cholesterol was measured by ELISA. Viral load and pathology were quantified by RTqPCR and immunohistochemistry. Finally, serum virus-neutralizing antibody levels were evaluated by haemagglutination inhibition. As observed previously, infected cholesterol-fed mice exhibited greater weight loss than diet matched controls. Total plasma cholesterol did not differ between diet groups. Infection increased the percentage of circulating granulocytes and decreased that of B cells at day 4 post-infection (p.i.). In contrast, diet did not affect circulating leukocytes. The amount of viral RNA at day 8 p.i. as well as serum neutralizing antibody levels were not affected by diet. Taken together, these data suggest dietary cholesterol affects the pathogenesis of influenza infection but prompt further study into better understanding the mechanism.