Metallomics Study of the molecular mechanism of trained immunity in primary immune cells

Abstract

By Kathleen Candor, Biochemistry ; Kavitha Subramanian Vignesh, University of Cincinnati

Advisor: Julio Landero Figueroa

Abstract: Trained immunity is defined as the overall capacity of innate immune cells to remember and alter their responses to a pathogen after previous exposure to a similar pathogen or a part of it. This highly relevant phenomenon is the basis of my research, I want to understand how critically important nutritional immunity is in this mechanism against intracellular fungal pathogen Histoplasma capsulatum (Hc). This process was done by isolating the bone marrow of mice, then the bone marrow would be stimulating for the growth of the Macrophage by using granulocyte macrophage-colony stimulating factor (GM-CSF). Then those macrophages were exposed to _-glucan, a surface marker common of several pathogens, for a seven-day time period. After those seven days, the macrophages were exposed to Hc for another seven days. The cells were then harvested, to have size-exclusion coupled with inductively coupled plasma-mass spectrometry (ICP-MS) was done on them to evaluate changes of zinc in trained Macrophage infected with Hc versus the untrained macrophages inflected with Hc. This project is still underway, the preliminary results show that pre-treatment with beta-glucan trains the macrophages and the result is an killing improvement of 60% vs control. We confirmed the role of Cu and Zn deprivation in this model .We can conclude that the amount of free Zinc in the macrophages that have been primed with beta-glucan decreased, and that is reflected in the Hc recovered.