A pair of scientists from Van Andel Institute and the National Institute of Allergy and Infectious Diseases have been granted a three-year, $1.5 million Allen Distinguished Investigator award from The Paul G. Allen Frontiers Group, a division of the Allen Institute, to better understand how diet and metabolism influence the immune system’s ability to fight off threats such as infections.

Established in 2016 by the late Microsoft co-founder and philanthropist Paul G. Allen, the Frontiers Group identifies researchers around the world whose work has the potential to accelerate scientific discoveries or launch entirely new avenues of exploration.

“We are deeply honored to receive this award, which allows us to seek critical insights about how our environment, particularly diet, affects immune responses,” Jones said. “Immune responses are like the tale of Goldilocks — they shouldn’t be too much or too little. By understanding the metabolic needs of immune cells, we hope to find that ‘just right’ balance that promotes highly effective immune responses without the damage that comes with an overactive immune response.”

The immune system is made up of many different types of cells, each tasked with a particular job to combat threats, protect the body and promote healing. To successfully carry out their functions, these cells rely on the body’s metabolism to provide them with the right kind of fuel at the right time.

If cells don’t receive enough fuel, the immune response can be insufficient. On the flip side, an overactive immune response can cause immune cells to attack healthy tissue.

Recent research by Jones and Belkaid revealed that T cells, a specialized type of immune cell that seeks and destroys sick cells, use several different types of fuel while at work. Jones and Belkaid aim to discover which types of fuel T cells prefer in hopes of finding ways to optimize their infection-fighting capabilities.

They also will explore how the microbiome — the vast population of helpful microbes that reside in the gut and aid in digestion — is influenced by diet and supports immune function. To date, the role of these bacteria in altering T cell metabolism during an immune response has been unclear.

Belkaid explained that the microbiota plays a fundamental role in the ability of the host to adapt to physiological changes, including those occurring during infection. She said part of this control occurs via microbiota derived “fuels” or adjuvants, and exploration of optimal immunity needs to be done in the context of these physiological metabolites.

In all, Jones and Belkaid’s project reflects a shift to viewing the immune system through the lens of its interactions with other systems in the body as well as outside influences.