Tarana Varshney
Pronouns: She/Her
Research Mentor(s): Patricia De Assis
Co-Presenter:
Research Mentor School/College/Department: Pathology / Medicine
Presentation Date: April 20
Presentation Type: Poster
Session: Session 6 – 4:40pm – 5:30 pm
Room: League Ballroom
Authors: Tarana Varshney, Patricia Assis, Ronald Allen, Steve Kunkel
Presenter: 14
Abstract
Recent studies have shown that sepsis survivors are more frequently readmitted to the hospital due to infections such as pneumonia or urinary tract infections, than their non-septic counterparts. This suggests that sepsis suppresses the immune response, however the mechanisms underlying this suppression are not well understood. The purpose of our study is to investigate the effects of sepsis on the function and proliferative ability of T-cells and to identify the epigenetic mechanisms involved in the long-term immunosuppression observed in sepsis survivors. Flow cytometry analysis of lymphocytes obtained from septic mice (day 1 and day 3) shows a drastic reduction in the absolute number of leukocytes, including T-cells, followed by recovery of these numbers in post-septic animals (day 28). That said, using a secondary infection model of pneumonia, we observed that CD4+ T-cells from post-septic mice produced significantly reduced concentrations of IFN-g and IL-17 and presented higher bacterial burden in the lungs compared to non-septic mice. Moreover, gene expression of MLL1, an important epigenetic regulator of CD4+ T-cell function, was downregulated in post-septic mice. Furthermore, in IFNAR deficient cells, MLL1 was found to be upregulated. These data suggest that impaired CD4+ T cell function in post-septic individuals may be regulated by chronic inhibition of MLL1 through the IFN-b-IFNAR pathway. Understanding the mechanisms of MLL1 suppression and T-cell dysfunction following sepsis can be used to develop treatments and therapies to prevent the secondary infection, and increase long-term quality of life for sepsis survivors.
Biomedical Sciences, Natural/Life Sciences
