Ex Vivo Immune Profiling in Patient Blood Enables Quantification of Innate Immune Effector Functions

Abstract

Assessment of a patient’s immune function is critical in many clinical situations. One prominent example is sepsis, which results from a loss of immune homeostasis due to microbial infection and is characterized by a plethora of pro- and anti-inflammatory stimuli that may occur consecutively or simultaneously. Thus, any immunomodulatory therapy would require in depth knowledge of an individual patient’s immune status at a given time. Whereas lab-test based immune profiling often relies solely on quantification of cell numbers, we have used an ex vivo whole-blood infection model in combination with biomathematical modeling to quantify functional parameters of innate immune cells in blood from patients undergoing cardiac surgery. These patients experience a well characterized inflammatory insult, which results in mitigation of pathogen-specific response patterns towards Staphylococcus aureus and Candida albicans that are characteristic for healthy people and baseline results in our patients. This does not only interfere with pathogen elimination from blood but also selectively augments the escape of C. albicans from phagocytosis. In summary, our model gives insight into immune functionality and might serve as a functional immune assay to record and evaluate innate response patterns towards infection.