For his work in furthering the understanding of how the human immune system senses dangerous invading pathogens, Bingxu Li has received the 2024 Michelson Philanthropies & Science Prize for Immunology. Li's prize-winning essay investigates the role that Stimulator of Interferon Genes, or STING, plays in including multiple distinct defenses against viruses, bacteria, and tumors and in orchestrating myriad downstream responses upon activation – resolving a significant mystery in the field of innate immunity. The sensing and clearance of invading pathogens are crucial to the survival of living systems, ranging from bacteria to humans. This is accomplished by an intricate web of innate immune receptors that detect pathogen-specific molecules called pathogen-associated molecular patterns (PAMPS). Once activated, these receptors trigger downstream immune responses designed to defend against the invading pathogen. However, some sensors exhibit additional behaviors upon activation. For example, activation of STING – a well-known human immune sensor – not only induces inflammation, but also triggers non-canonical autophagy, inflammasome activation, and cell death, thus inducing multiple defenses against different types of pathogens. How STING controls these diverse downstream responses has remained unknown. Using various genetic, biochemical, and structural tools, Li and his colleagues at the Massachusetts Institute of Technology discovered that human STING plays a surprising role as an ion channel. To the author's knowledge, it is the first ion channel that is known to sense danger in mammalian cells. Furthermore, the discovery hints at the adaptability of innate immune proteins like STING, suggesting that they have evolved to acquire diverse new functions over time, without drastic changes.
Finalists for the prize were Gabriele Casirati for his essay "Stem cells in disguise: How epitope editing can empower targeted cancer immunotherapies," and Carla Nowosad for her essay "Who goes there? How B cells assess risk in the intestine."
