Dysfunctional Myelopoiesis and Myeloid-Derived Suppressor Cells in Sepsis Pathobiology Subtitle: Pathological Myeloid Activation After Sepsis and Trauma
University of Florida
Summary
Adverse outcomes in surgical sepsis patients are secondary to dysregulated emergency myelopoiesis, and expansion of myeloid-derived suppressor cells. Here we propose to determine the underlying mechanisms behind the increased expansion of these leukocyte populations and the underlying mechanisms that drive inflammation and immune suppression.
Description
Our overarching hypothesis is that the consequences of surgical sepsis (death and poor quality of life) are the result of an unresolving host leukocyte dyscrasia, similar to other chronic conditions such as cancer and autoimmune disease. Specifically, the preferential expansion and self-perpetuation of myeloid-derived suppressor cells (MDSCs), propagated in part through epigenetic changes in both bone marrow (BM) progenitors and MDSCs, drives non-acute infectious and noninfectious complications after sepsis. This Program will investigate in human surgical sepsis the underlying mechanisms that…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- Yes
Sepsis participant: Inclusion Criteria: 1. age ≥18 years 2. meets criteria for sepsis/septic shock by Sepsis-3 consensus criteria. Exclusion Criteria: 1. have disease states that predispose to significant immune system dysfunction 2. have comorbidity burden or goals of care that preclude recovery after sepsis. These criteria include: a. irreversible shock (death \<12 hours) b. uncontrollable surgical source of sepsis c. patients deemed to be futile care or have advanced directives limiting resuscitative efforts d. alternative diagnoses causing shock state (e.g., hemorrhage, myocardial…
Interventions
- OtherBlood sampling
Blood sampling
Location
- UF Health at Shands hospitalGainesville, Florida