Tracy Toliver-Kinsky, Ph.D., Assistant Professor
Severe burn patients are susceptible to nosocomial infections that can delay wound healing, increase hospitalization, and lead to sepsis. Despite aggressive infection control, sepsis remains a leading cause of mortality in patients that survive the initial burn injury. This is due not only to loss of the skin as a protective barrier, but also to burn-induced alterations in the functions of most immune cells. The main goals of our research are to understand the mechanisms by which severe burn injury increases susceptibility to infections, and to investigate immunomodulatory strategies that may increase resistance to infections after trauma.
Current research efforts are focused on the use of a hematopoietic cytokine and dendritic cell growth factor, fms-like tyrosine kinase-3 ligand (Flt3L), as a prophylactic treatment after burn injury to stimulate the production of new progenitor cells that give rise to dendritic cells. Dendritic cells are antigen presenting cells that reside in tissues that frequently encounter pathogens and, upon recognition of microorganisms, trigger responses that are central in the activation and regulation of both innate and acquired immunities. Therefore, our hypothesis is that stimulation of dendritic cell production and/or functions after burn injury can increase resistance to infections. We have found that treatment with this cytokine increases survival in a model of burn wound infection, decreases bacterial growth and spread, and enhances Th1 cytokine responses to systemic bacterial challenge. Interestingly, these protective effects can be conferred to non-treated recipient mice by the adoptive transfer of dendritic cells from Flt3L-treated donors, but not non-treated donors. This indicates that Flt3L modulates some dendritic cell properties, enhancing their ability to clear wound infections. We are currently examining the effects of Flt3L on dendritic cell functions and the role that dendritic cells may play in wound healing. In vivo models of experimental injury and infection are employed to assess local and systemic responses by a variety of molecular, cellular, and immunological techniques. By integrating multiple aspects of whole animal biology, we hope to gain insight into the mechanisms by which severe burn injury impacts immune function and to develop potential immunomodulatory interventions to prevent infections after burn injury.
