Thomas Griffith, PhD, professor in the University of Minnesota Department of Urology and a member of the Center for Immunology and Cancer Immunology, has been awarded a $2.6 million renewal grant from the National Institutes of Health (NIH) to continue investigating how sepsis affects the immune system and increases patients' risk of future infections.
Sepsis is a life-threatening condition that occurs when the body's response to infection causes widespread inflammation and organ dysfunction. Consequently, many of the nearly two million Americans that develop sepsis every year will experience long-term immune system problems that leave them vulnerable to additional infections, repeated hospitalizations, and higher mortality rates.
Dr. Griffith and his research team are working to better understand why these immune complications occur. The project focuses on how sepsis alters the function of T cells and B cells, critical components of the immune system responsible for fighting infections and developing long-term immune protection.
The research addresses a critical challenge in sepsis care. During the early stages of sepsis, the immune system often becomes hyperactivated, releasing large amounts of inflammatory signaling molecules. This initial inflammatory response is followed by a dramatic loss of immune cells, known as lymphopenia, leaving the body in a prolonged state of immune suppression, or "immunoparalysis." This long-term immune dysfunction is believed to be a major reason why sepsis survivors experience recurrent infections and poorer long-term outcomes compared with other critically ill patients. The resulting healthcare costs, including repeated hospital admissions and intensive care stays, place a significant burden on patients, families and healthcare systems.
“Many sepsis survivors face ongoing immune dysfunction long after they leave the hospital,” said Griffith. “By identifying the cellular and molecular changes that occur after sepsis, we hope to develop more precise approaches to restoring immune health and reducing the risk of recurrent infections.”
The research team will use a combination of phenotypic, functional, genomic, and metabolic assays to identify the mechanisms that drive immune dysfunction following sepsis. The findings could help explain why previous attempts to treat sepsis-related immune suppression have had limited success and may pave the way for more personalized therapies tailored to a patient’s specific immune status.
The project brings together an interdisciplinary team of experts from the University of Minnesota and leading research institutions across the country. University of Minnesota collaborators include Robert Gould, MD, of the Department of Anesthesiology; Steven Shen, PhD, of the Institute for Health Informatics; and T. Dileepan, PhD, of the Department of Microbiology and Immunology. The broader research team also includes Scott Brakenridge, MD, of the University of Washington; Vladimir Badovinac, PhD, of the University of Iowa; Kenneth Remy, MD, of Case Western Reserve University; and Richard Hotchkiss, MD, of Washington University in St. Louis.
The grant, "CD4 T Cell Dysregulation and Reprogramming in Sepsis," will support research through March 31, 2031.