What does eating a lot of fast food do to your immune system?
According to the findings, even changing to a healthful diet does not seem to undo the damage.
The long-term changes may contribute to type 2 diabetes, arteriosclerosis, and several other conditions wherein inflammation is thought to play a part, and which have been linked to consumption of a Western diet.
For the study, the researchers fed atherosclerosis-prone mice on a Western diet comprising high-calorie, high-fat, low-fiber, and fast food.
The Western diet altered gene expression
After just 1 month, the mice showed changes throughout their bodies that are similar to the strong inflammation reactions that occur in bacterial infections.
"The unhealthy diet," says lead study author Anette Christ, a postdoctoral fellow at the University of Bonn, "led to an unexpected increase in the number of certain immune cells in the blood of the mice, especially granulocytes and monocytes."
This led the team to explore what might be happening further upstream, in the bone marrow, where the precursors, or progenitors, of these particular types of immune cell are located.
The researchers compared major immune cell bone marrow progenitors from mice that had been fed on a Western diet with those of control mice that had been fed on a more healthful, normal cereal diet.
They found that the Western diet had switched on many genes in the progenitor cells, including some that increase proliferation and enhance responses from the innate immune system.
The innate immune system is a part of the immune system that reacts with a rapid, broad response to infection, which is later followed by a more specific reaction from the adaptive immune system.
Healthful diet did not reverse gene activation
The acute inflammation response died down in the Western diet mice after they were placed on their normal cereal diet for 4 weeks.
But switching to the more healthful diet failed to reverse the fundamental alterations in the innate immune system, and many of the genes that had been activated by the Western diet stayed active.
"It has only recently been discovered," notes senior study author Prof. Eicke Latz, the director of the Institute for Innate Immunity of the University of Bonn, "that the innate immune system has a form of memory."
There is a process called "innate immune training," he explains, which is normally triggered by bacterial infection, but in the case of the mice in the study, it was triggered by a Western diet.
Innate immune training ensures that after infection, the body remains "in a kind of alarm state," so its defenses can "respond more quickly to a new attack," Prof. Latz adds.
Protein sees the Western diet as a pathogen
The team also discovered that a protein called NLR family pyrin domain containing 3 (NLRP3) is the immune system sensor that recognizes the Western diet as a pathogen and therefore triggers the inflammatory response.
In addition, it seems that as well as triggering inflammatory responses through NLRP3, the Western diet also causes long-term epigenetic changes in the packaging of genetic material, so that parts of DNA that are normally difficult to access are easier to read.
"The immune system consequently reacts even to small stimuli with stronger inflammatory responses," explains Prof. Latz.
In a final set of tests, the team confirmed the role of NLRP3 by showing that mice bred to lack the protein did not develop systemic inflammation from a Western diet, and neither did they show some of the other longer-term changes involving the protein.
The researchers conclude that NLRP3 brokers the trained immunity that follows from a Western diet and "could thereby mediate the potentially deleterious effects of trained immunity in inflammatory diseases."
Prof. Latz says that the findings highlight the dramatic impact that the wrong kind of food can have, and that they have important implications for society.
"Children have a choice of what they eat every day. We should enable them to make conscious decisions regarding their dietary habits," he adds.
"The foundations of a healthy diet need to become a much more prominent part of education than they are at present."
Prof. Eicke Latz