12 Jan 2018 --- The immune system reacts similarly to a high fat and high-calorie diet as to a bacterial infection, according to a study by the University of Bonn. What is particularly disturbing is that unhealthy food seems to make the body's defenses more aggressive in the long term. Even long after switching to a healthy diet, inflammation towards innate immune stimulation is more pronounced, the researchers found. These long-term changes may be involved in the development of arteriosclerosis and diabetes, diseases linked to Western diet consumption. The results are to be published in the journal Cell.

The scientists placed mice for a month on a so-called “Western diet”: high in fat, high in sugar and low in fiber. The animals consequently developed a strong inflammatory response throughout the body, almost like after infection with dangerous bacteria.

“The unhealthy diet led to an unexpected increase in the number of certain immune cells in the blood of the mice, especially granulocytes and monocytes. This was an indication for an involvement of immune cell progenitors in the bone marrow,” explains Anette Christ, postdoctoral fellow in the Institute of Innate Immunity of the University of Bonn.

To better understand these unexpected findings, bone marrow progenitors for major immune cell types were isolated from mice fed a Western diet or healthy control diet and a systematic analysis of their function and activation state was performed.

“Genomic studies did, in fact, show that the Western diet had activated a large number of genes in the progenitor cells. The genes affected included those responsible for proliferation and maturation,” explains Prof. Dr. Joachim Schultze from the Life & Medical Sciences Institute (LIMES) at the University of Bonn and the German Center for Neurodegenerative Diseases (DZNE).

Fast food thus causes the body to quickly recruit a huge and powerful army. When the researchers offered the rodents their typical cereal diet for another four weeks, the acute inflammation disappeared. What did not disappear was the genetic reprogramming of the immune cells and their precursors: Even after these four weeks, many of the genes that had been switched on during the fast food phase were still active.

“It has only recently been discovered that the innate immune system has a form of memory,” explains Prof. Dr. Eicke Latz, Director of the Institute for Innate Immunity of the University of Bonn and scientist at the DZNE. “After an infection, the body's defenses remain in a kind of alarm state, so that they can respond more quickly to a new attack.” Experts call this “innate immune training.” In the mice, this process was not triggered by a bacterium, but by an unhealthy diet.

The scientists were further able to identify the responsible “fast food sensor” in immune cells. They examined blood cells from 120 subjects. In some of the subjects, the innate immune system showed a particularly strong training effect. In these subjects, the researchers found genetic evidence of the involvement of a so-called inflammasome. Inflammasomes are key intracellular signaling complexes that recognize infectious agents and other harmful substances and subsequently release highly inflammatory messengers. How exactly the NLRP3 inflammasome recognizes the exposure of the body to Western type diets remains to be determined.

Interestingly, in addition to the acute inflammatory response, this also has long-term consequences for the immune system's responses: The activation by Western diet changes the way in which the genetic information is packaged. The genetic material is stored in the DNA and each cell contains several DNA strands, which together are about two meters long. However, they are typically wrapped around certain proteins in the nucleus and thus many genes in the DNA cannot be read as they are simply too inaccessible.

Unhealthy eating causes some of these normally hidden pieces of DNA to unwind, similar to a loop hanging out of a ball of wool. This area of the genetic material can then be read much easier as long as this temporary unwrapping remains active. Scientists call these phenomena epigenetic changes. “The inflammasome triggers such epigenetic changes,” says Dr. Latz. “The immune system consequently reacts even to small stimuli with stronger inflammatory responses.”

These inflammatory responses can in turn accelerate the development of vascular diseases or type 2 diabetes. In arteriosclerosis for example, the typical vascular deposits, the plaques, consist largely of lipids and immune cells. The inflammatory reaction contributes directly to their growth, because newly activated immune cells constantly migrate into the altered vessel walls. When the plaques grow too large, they can burst, leading to blood clotting and are carried away by the bloodstream and can clog vessels. Possible consequences: Stroke or heart attack.