How Nutrition Affects the Immune System's Ability to Fight Infection

According to a recent study published in Cell, people’s food preferences during times of sickness may be linked to the type of infection they have and to the type of food the immune system needs to combat the infection.

“We found that, whereas glucose utilization was required for survival in models of viral inflammation, it was lethal in models of bacterial inflammation,” write Andrew Wang, MD, PhD, Yale University School of Medicine, and colleagues.

Sickness behaviors are adaptations that are considered to help animals survive acute infections. Anorexia of infection, for example, is a common behavioral response to infectious diseases. Yet, despite extensive research investigating the role of nutrition in sepsis, the underlying mechanism of this behavior remains unknown.

Nevertheless, understanding the biology of such sickness behaviors is important to improve management of critically ill patients who have conditions such as sepsis, the authors say. With this in mind, the researchers set out to investigate the role of anorexia in bacterial and viral infections. Using lab mice, they examined the effects of providing supplementary nutrients during infection.

First, to examine the role of anorexia in infection, the researchers infected mice with the bacterium Listeria monocytogenes, a common cause of food poisoning. They found that these infected mice stopped eating, but eventually recovered. However, when the researchers supplemented Listeria-infected mice with food by force-feeding them, the mice died. “We found that anorexia was protective while nutritional supplementation was detrimental in bacterial sepsis,” they explain.

Next, they aimed to determine what component of the food was responsible for this lethal effect. They found that although Listeria-infected mice survived the infection when they were fed fats or proteins, they died when they were fed glucose. To confirm that the lethal effect was due to glucose, the researchers gave glucose to some Listeria-infected mice and then treated them with 2-deoxy-D-glucose (2DG), a chemical which blocks glucose uptake by the body’s cells; these mice survived the infection.

“We next asked whether viral infections, which induce a different type of immune response compared to bacterial infections, were also affected by caloric supplementation,” the authors write. They infected mice with influenza virus A/WSN/33 and found that these animals also developed anorexia. However, when the researchers supplemented influenza-infected mice with food by force-feeding them glucose, the mice survived. Mice that did not receive nutritional supplementation died, as did those that were infected with the virus and then treated with 2DG.

“[W]hereas nutritional supplementation increased mortality of Listeria monocytogenes infection, it protected against lethality of influenza virus infection,” the authors note.

These effects were also mostly independent of pathogen burden and extent of inflammation. Instead, the researchers found that the two types of infection affected different regions of the brain, suggesting that the metabolic needs of the mice differed depending on which part of the immune system was stimulated.

In a news release on the Yale University website, the study’s lead contact, Ruslan M. Medzhitov, PhD, emphasized that bacterial and viral infections cause different types of inflammation that can lead to tissue damage, and, depending on the cause of the infection, nutrition can therefore either increase or decrease the body’s ability to tolerate inflammation. “During a viral infection, eating provides glucose, which may be necessary for survival,” Dr. Medzhitov said. In contrast, fasting leads to the production of ketones, another type of fuel which may help animals tolerate a bacterial infection, he added.

According to the authors, the results of this study suggest “a differential need for metabolic fuels as a function of infection (or inflammation) class and sheds light on the biology behind the old adage ‘starve a fever, stuff a cold.’”

“Much work will need to be done to identify how organismal metabolism is coordinated in other infectious and inflammatory states and whether or not these findings can be extended to humans in the management of inflammatory diseases and critical illness,” they conclude.

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.