This experience gave Talbot an appreciation for the importance of studying these interactions. However, long-term, Talbot wanted to focus on human health and the role that environmental factors can have on our immune system. After a brief experience with research in human genetics, he pursued a master’s and doctoral degrees studying how environmental factors contribute to the aggravation of immune disorders, such as rheumatoid arthritis. His research found the molecular links between exposure to environmental pollutants and the disruptions they cause to the immune system, resulting in chronic inflammation.
As Talbot started his postdoctoral research, he became interested in emerging evidence suggesting that our nervous systems and immune systems may be talking to each other.
“It was fascinating,” he said. “Because this would suggest that immune cells were communicating with neurons and that neurons could be participating in immune responses.”
Excited by this potential, Talbot dug deeper. He focused his research on a specific group of immune cells in the gut, finding they often cluster around neurons. These immune cells are responsible for controlling the formation of a layer of mucus in the gut called the intestinal barrier. Talbot suspected that the neurons may be activating the immune cells and boosting their function. But instead — to his surprise — he found that the gut neurons inhibited these cells.
“This was confusing at the time,” he said, “Why would you have neurons that inhibit the function of immune cells that protect the host against infection?”
"It was fascinating because this would suggest that immune cells were communicating with neurons and that neurons could be participating in immune responses."
This intriguing result would ultimately be explained by the body’s need to balance multiple, sometimes competing, priorities: bringing in nutrients from our diet while keeping harmful things out.
“These immune cells live inside of the gut and secrete proteins that increase the barrier of the intestine,” Talbot said. “By increasing the gut barrier, you help prevent pathogens from causing an infection. The problem is that the gut’s main function is to absorb nutrients, so by increasing the barrier, you’re reducing the efficiency of nutrient absorption."
He found that these neurons detect the presence of food and then inhibit the immune cells, temporarily reducing the intestinal barrier. As a result, the body absorbs more nutrients, including fat. In the absence of food, the neurons are not active, which frees the immune cells to increase the intestinal barrier and help protect the body from infection.
In his lab at Fred Hutch, Talbot continues his research into how the nervous and immune systems work together to balance the competing needs of absorbing nutrients and preventing infection. His work helps reveal the signals that drive these interactions and the mechanisms behind how pathogens can highjack the nervous system to enable infection. Talbot is excited about where these discoveries will lead and their potential impact on human health.
“Our research might not only help to find new ways of treating gut infections, but also reveal new forms of therapy for malnutrition and metabolic disorders,” he said.
— By Matthew Ross, Nov. 30, 2021