September 14, 2018

Drs. Vladimir Badovinac and Kevin Legge were awarded a Carver Trust Collaborative Pilot Grant from the College of Medicine entitled “Impairment and Recovery of Dendritic Cell Immunity after Sepsis”. The goal of the grant is to further define functional consequences imposed on critical components of adaptive immunity and dendritic cell (DC) biology following sepsis induction. The two year award started July 1, 2018 with total funding of $50,000.

The outcome of viral or bacterial infections is determined by a series of complex interactions between the pathogen and infected host. Among those interactions, the immune status of the host at the time of pathogen encounter can have a major impact on susceptibility to disease. Sepsis strikes 750,000 Americans annually, and 20-30% of these patients die – far more than from prostate cancer, breast cancer, and AIDS combined. Patients that survive sepsis often display severely compromised immune functions with deficits in innate and adaptive responses. One hallmark of the general immunosuppression (or immunoparalysis) observed during polymicrobial sepsis is diminished DC function and T cell immunity. Consequently, septic patients and sepsis survivors are highly susceptible to new or previously encountered infections that are readily controlled by T cells when a normal, functioning immune system is present. Thus, the funds from this grant will be used to address the central hypothesis that sepsis-induced apoptosis of precisely defined DC subsets leads to long-lasting deleterious changes in the composition and/or function of the DC compartment. These DC lesions can in turn result in diminished CD4 and CD8 T cell responses to newly or previously encountered antigens delivered in the context of localized or systemic infections.