Background Info
An invasive fungal infection that initiates inflammatory and immunosuppressive responses
An unstable molecule that contains oxygen and easily reacts with other molecules in a cell
(too much may cause genetic cell damage and induce cell death)
What is apoptosis?
Programmed cell death
What are cytokines?
Signaling proteins that regulate inflammation
What is the overarching conclusion the experimenters gathered?
The combination of resveratrol and micafungin may be an effective treatment for C. glabrata infection
What is phagocytosis and how do macrophages contribute to this process?
Phagocytosis is the process by which a cell ingests and kills particles
Macrophages are cells that participate in innate immune responses (remove debris and pathogens) via performing phagocytosis
What is the difference in ROS production in normal macrophages vs macrophages co-cultured with Candida (Panel A)?
↑ ROS production when Candida is present
Candida’s effect on ↑ ROS production gets exacerbated with time
How was apoptosis measured in this study?
Via dual-staining patterns and flow cytometry
What do the numbers/letters at the top of each bar graph represent?
Different inflammatory cytokine markers
What is micafungin's role in treating C. glabrata infection?
Micafungin inhibits C. glabrata cell proliferation
What are the four DVs the experimenters measured across varying treatment concentrations of resveratrol?
cell proliferation, apoptosis, ROS, and inflammatory gene expression of macrophages
What is the overall relationship between resveratrol concentration and ROS production (Panel B)?
The higher the resveratrol concentration, the less ROS production
How does apoptosis percentage trend across varying concentrations of resveratrol?
As the resveratrol concentration ↑, the apoptosis percentage ↓
What is the overall relationship between resveratrol concentration and cytokine expression?
↑ resveratrol concentration means ↑ cytokine expression
How does resveratrol affect ROS production?
higher resveratrol concentration reduces ROS production and cell damage
What are 3 of the main pathogenic factors of Candida?
adhesion, biofilm formation, oxidation resistance, production and secretion of hydrolases
What is the relationship between resveratrol concentration and ROS production as time proceeds?
The higher the resveratrol concentration, the less ROS production BUT resveratrol is a tad less effective at reducing the ROS production as time proceeds (24h → 48h)
What does the staining figure tell us about the apoptosis trend?
As resveratrol concentration increases, the percentage of macrophage cells that are apoptotic decreases. This can be seen in the upper right quadrants as they signify the number of macrophage cells that were double stained for apoptosis across concentrations.
(Staining correlates to presence of apoptosis)
How does resveratrol affect apoptosis of macrophages?
resveratrol can maintain normal physiologic homeostasis via regulating apoptosis of macrophages
What is micafungin and what is its MOA?
Micafungin is an echinocandin drug that treats patients with BSIs (antifungal medication)
MOA: inhibits synthesis of D-glucan in the fungal cell wall (decreasing fungal activity and enhancing killing ability of macrophages)
With resveratrol being dose-dependent, what are its effects at low vs high concentrations on ROS production? Name one result/example at each concentration.
Low = beneficial (promotes signal transduction, cell response, and repair)
High = harmful (impairs normal functioning of tissues/organs)
How does resveratrol promote generation of pro-inflammatory cytokines?
high concentrations of resveratrol shifts macrophage phenotype to pro inflammatory (M2) & promotes killing ability of macrophages via upregulating GSDMD expression