Dietary Cholesterol Exacerbates Influenza Mice Inflammation, Disease–ScienceDaily

A new study from the University of Illinois suggests that high levels of dietary cholesterol can make mice sick when infected with the flu. This study is the first to link dietary cholesterol to exacerbation of viral infections.

Previously, scientists associated a high-fat diet and elevated blood cholesterol with increased susceptibility to infections and decreased immune response. For example, obesity is a well-known risk factor for severe COVID and influenza illnesses. However, few studies have isolated the contribution of cholesterol to these infections and none have described the effects of dietary cholesterol.

“High serum cholesterol levels can increase the risk of sepsis in influenza infections, and we found that statins (cholesterol-lowering drugs) can improve survival for influenza pneumonia, SARS-CoV-2 infections, and sepsis. But it wasn’t. Clarify if or how cholesterol in the diet was involved. ” Journal of Immunology Research and PhD student in the Illinois Neuroscience Program.

Cholesterol is essential to the body. It is part of our cell membrane, helps us make hormones and vitamin D, and enables proper immune cell function. Our body manufactures it for us and there is little need to enter from a dietary source. In fact, for healthy people, dietary cholesterol has virtually no effect on circulating cholesterol levels and does not increase the risk of cardiovascular disease. This is part of the reason why cholesterol intake restrictions were lifted from American dietary guidelines in 2015.

However, when it comes to mouse infections, Louie’s research suggests that dietary cholesterol can make a difference without increasing dietary fat.

Louie, along with co-authors Andrew Steelman and Joseph Tingling, fed mice a standard rodent feed or the same diet supplemented with 2% cholesterol. Five weeks after feeding, the mice were infected with the human influenza A virus adapted to the mice. The research team tracked the progression of the disease, including weight loss, food intake, and disease behavior. They also tracked serum cholesterol levels and immune responses and measured lung viral load at multiple points in the course of infection.

“Cholesterol-fed mice consistently had higher prevalence across four cohorts,” says Louie. “They showed greater weight loss and sick behavior.”

A high-cholesterol diet could increase the viral load in the lungs, as the virus also requires cholesterol for cell invasion and replication. But that wasn’t what the researchers found.

“Our plaque assay did not show a significant difference in viral load in the lungs of the two groups of mice,” said Tingling, a postdoctoral fellow at the Illinois School of Animal Science. “It is very important to consider the host’s immune system as well as the infectious pathogen.”

As for the host, researchers have determined that mice fed a high-cholesterol diet are ill because of a malfunctioning immune system. Fat can have immunosuppressive effects, which are harmful during the course of infection. However, an inadequate immune system has not been observed by researchers in cholesterol-fed mice. Instead, cholesterol increased the number of cytokine-producing immune cells in the lungs.

“The so-called cytokine storm during severe illness causes excessive inflammation that can damage the host. Along these lines, the lungs of cholesterol-fed mice produce more cytokines. It turns out that the cells are infiltrating. I’m sick, “says Loei. “It’s a double-edged sword. You want to be able to initiate an effective immune response, but excessive inflammation is harmful.”

Unfortunately, the effects of dietary cholesterol on influenza prevalence continued long after mice stopped eating it. The researchers first ate mice that had a high-cholesterol diet and then fed a normal diet for five weeks. When those mice were exposed to the flu, they were still sick than mice that had never eaten a high-cholesterol diet.

“We thought this dietary ingredient was a highly modifiable factor. Perhaps it had only a temporary effect, but in the end, another five weeks on a regular diet with cholesterol. It turns out that it’s not enough time to completely undo the harmful effects, “says Louie. ..

Surprisingly, inflammatory changes in the lungs were detectable in high-cholesterol mice, even before infection with influenza.

“Some of the changes in lung immune function were already present before infection. It would be interesting to see exactly how dietary cholesterol increased inflammation before infection,” he said. Corresponding author Steelman, an associate professor of the Department of Animal Science in Neuroscience, says. Program, and the Department of Nutrition Science in Illinois.

“Nevertheless, our data summarize that dietary cholesterol increased the prevalence of influenza-infected mice. The response occurs in the lungs, not the effects of the virus itself. Appeared to be the result of an abnormal immune response that indicates that these results need to be considered. How host factors contribute to the outcome of the disease. “

The School of Agriculture and Animal Science belongs to the Faculty of Agriculture, Consumers and Environmental Sciences at the University of Illinois at Urbana-Champaign.

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