The research of Kathryn A. Knoop, Ph.D., explores mucosal immunology and how gut-residing bacteria contribute to the development of the immune system. Early life is an important time to establish oral tolerance to proteins from the diet or from the microbiota, and disruption to these processes can result in inflammatory or allergic disorders.
Several factors ranging from maternal proteins in breast milk and microbial ligands from the microbiota regulate the development of oral tolerance in early life. The laboratory of Dr. Knoop combines genetic and cell biological approaches to investigate systemic and tissue-specific immune responses to dietary proteins and enteric infections during these unique phases of early life.
- Maternal regulation of mucosal immunity in offspring. Several components in breast milk are present exclusively or at high levels in the first days following birth. These may promote mucosal immunity in the offspring by strengthening the epithelial barrier and preventing bacterial translocation. Dr. Knoop's lab is investigating the components in breast milk that prevent luminal translocation of antigens in neonates and the consequences of antigen translocation in neonates.
- Bloodstream infections resulting from gut-residing bacteria. During the neonatal phase of life, the intestinal microbiota is relatively simple and composed of small Gram-negative bacteria. Some of these species can cross the epithelium and circulate throughout the body. Risk factors include being born prematurely and lacking access to breast milk. Once across the intestinal epithelium, bacteria can cause bloodstream infections. The severity of such infections is dependent on the age of the offspring, with those closer to birth developing more-severe inflammatory responses resulting in neonatal sepsis. Dr. Knoop's lab is investigating how the immune system responds to gut-residing pathogen changes during the neonatal phase of life.
- Induction of oral tolerance during early life. As offspring grow during infancy, maternal components in breast milk that prevent antigen translocation become reduced and allow luminal antigens to translocate to the immune cells within the intestinal lamina propria. This process is vital for the induction of oral tolerance. Dr. Knoop's lab is investigating the components supporting the induction of tolerance to oral antigens and the consequences of preventing antigen translocation during this time.
Significance to patient care
The relationship the body maintains with the gut-residing bacteria making up the microbiota has important implications for several key health outcomes. Proper establishment of this relationship occurs during early life, and understanding what factors contribute to this process is key to maintaining long-term immune health through adulthood. Dr. Knoop's lab is investigating factors regulating this process, and how some gut-residing pathogens may be able to subvert this process and disseminate to the body, resulting in bloodstream infections and sepsis.