Quantifying the Effect of Vitamin D Deficiency and Alcohol Exposure on Immune Response to Mycobacterium Infection

The goal of the May Multiscale Immunobiology Design, Algorithms, & Simulation (MIDAS) Lab is to develop dynamic empirical and simulation-based models of host-pathogen interactions to further our understanding of the mechanisms guiding immunologic response. Previous studies on the role of vitamin D3 and its modulation of host response have shown increased anti-inflammatory cytokines and effector substrates during innate immune response; however, many of these studies investigated only single, often dissimilar, levels of infection[1]–[8]. There is currently not a well-established model of macrophage immune modulation by vitamin D3 and the data regarding the kinetics of this process are scarce. There remains a need for more quantitative data on the dynamic impact of vitamin D3 on host response to infection [3], [5]. The majority of studies collected samples and investigate the host response at a single, usually end-stage, time point versus quantifying vitamin D3’s modulation of the host response throughout the study. Furthermore, minimal consideration has been given to the potential immune modulatory effects of the vehicle and biochemical process through which vitamin D3 is delivered [3], [9]. This results in a lack of empirical dynamic data that takes into consideration state of host prior to and during infection/treatment. The objective of our lab’s research is to develop in vitro, ex vivo, and in silico models that can capture host state, quantifying and expounding on the mechanistic differences in immunologic response due to host state. The focus of my doctoral research is the investigation of host vitamin D3 deficiency in conjunction with adolescent immune response and alcohol exposure. This research will provide insight into the ramifications of age-related vitamin D3 deficiency and its effect on the outcome of mycobacterium infection, as well as, the combined effects of vitamin D3 deficiency and alcohol exposure on infection outcome. This platform can be expanded upon in the future to aid in the identification of immunomodulator associated therapies to enhance host immune response to TB.