As respiratory illness season continues, the familiar discomfort of a sore throat, fatigue, and a desire to cancel plans is widespread. But beyond these common symptoms, a fundamental question remains: what exactly *is* sickness, and why do our bodies respond the way they do when fighting off infection? New research at the Massachusetts Institute of Technology (MIT) is beginning to unravel the complex interplay between the brain and the immune system that underlies these responses, suggesting that “sickness behavior” isn’t simply an unfortunate side effect of illness, but a potentially adaptive defense mechanism.
Zuri Sullivan, a new assistant professor in the MIT Department of Biology and a core member of the Whitehead Institute for Biomedical Research, is leading this investigation. Her work focuses on the biological processes at the intersection of neuroscience, microbiology, physiology, and immunology. Sullivan’s research aims to understand how the brain and immune system communicate to generate changes in behavior and physiology during infection, such as fever, loss of appetite, and social withdrawal. Understanding these mechanisms—the field of neuroimmunology—could have significant implications for how we approach and treat infectious diseases.
Immunity: More Than Just Fighting the Pathogen
Sullivan frames immunity not as a single process, but as two distinct, yet interconnected, strategies. “We can believe of immunity in two ways: the antimicrobial programs that defend against a pathogen directly, and sickness, the altered organismal state that happens when we receive an infection,” she explains. This perspective shifts the focus from solely eliminating the invading pathogen to understanding the broader physiological changes that occur during illness.
Traditionally, sickness has been viewed as an unintended consequence of the immune system’s activity. However, Sullivan’s research suggests a more active role. “People might assume that sickness is an unintended consequence of infection, that it happens given that your immune system is active, but we hypothesize that it’s likely an adaptive process that contributes to host defense,” she says. This hypothesis proposes that behaviors like reduced appetite and increased sleep aren’t simply symptoms, but rather actively contribute to survival by conserving energy and bolstering the immune response.
The Allure of Sickness Behaviors: Appetite and Sleep
Sullivan’s interest in sickness behaviors stems from her earlier work at Yale University, where she studied the gut microbiome and its interaction with the immune system. She found herself particularly drawn to the connection between food, immunity, and the brain. “I’m especially interested in the interaction between food, the immune system, and the brain. One of the things I’m most excited about is the reduction in appetite, or changes in food choice, because we have what I would consider pretty strong evidence that these may be adaptive,” she stated. The idea that altering dietary habits during illness could be a beneficial response, rather than a debilitating symptom, is a key focus of her research.
Sleep is another area of intense interest. The near-universal experience of altered sleep patterns during illness—whether it’s increased sleepiness or disrupted rest—suggests a fundamental link between infection and the brain’s sleep-wake regulation. Sullivan emphasizes the importance of studying these changes over the course of an infection, recognizing that individual responses and pathogen dynamics can introduce variability. “I also don’t just want to examine snapshots in time. I want to characterize changes over the course of an infection,” she explained. “There’s probably going to be individual variability, which I think may be in part because pathogens are also changing over the course of an illness — we’re studying two different biological systems interacting with each other.”
Building a Collaborative Research Program
Sullivan’s approach to research is inherently collaborative. She is actively building a team and forging partnerships with other researchers at MIT and the Whitehead Institute. She’s seeking individuals with creative thinking and diverse expertise, particularly those who can bridge the gap between different biological disciplines. “I really want to bring together different areas of biology to think about organism-wide questions,” she said. “The thing that’s most important to me is people who are creative.”
One existing collaboration is with Sebastian Lourido’s lab, where they are investigating how Toxoplasma gondii, a common parasite, influences social behavior. Sebastian Lourido’s research focuses on the molecular mechanisms of host-pathogen interactions. Sullivan is also eager to collaborate with Siniša Hrvatin’s lab, which studies molecular neuroscience and the mechanisms underlying torpor—a state of decreased physiological activity. Siniša Hrvatin’s work on the hypothalamus, a brain region crucial for regulating homeostatic behaviors, aligns directly with Sullivan’s interest in understanding how the brain controls physiological changes during sickness.
By studying sickness states induced by a variety of pathogens—including parasites, viruses, and bacteria—Sullivan hopes to identify common principles governing the brain-immune interaction. “By studying different sickness states generated by different kinds of pathogens — parasites, viruses, bacteria — we can ask really compelling questions about how and why we get sick,” she said.
Disclaimer: This article provides information for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
The research at MIT promises to deepen our understanding of the complex relationship between infection, immunity, and behavior. The next step for Sullivan’s lab will be to recruit talented researchers and expand these collaborative efforts, paving the way for new insights into how we respond to illness and potentially leading to novel therapeutic strategies. Share your thoughts on this fascinating research in the comments below.
