Metals and Host Control of Histoplasma capsulatum
George S. Deepe, Jr., MD
Professor of Medicine
Division of Infectious Diseases
University of Cincinnati College of Medicine
Histoplasma capsulatum is the most frequent cause of fungal respiratory illness in the United States. This dimorphic fungal pathogen is endemic to the Midwestern and Southeastern US and Central and South America. The organism is an emerging pathogen in Asia. Mammals inhale spores present in soil, and these fungal elements transform into the pathogenic yeast phase once they have entered lungs. Innate and adaptive immunity are critically important in fungal elimination. The organism thrives in macrophages, but not dendritic cells or neutrophils. Activation of macrophages by cytokines such as interferon-g or granulocyte macrophage colony-stimulating factor (GM-CSF) halts the intracellular growth of this fungus. On the other hand, interleukin-4 promotes fungal survival within macrophages. We have discovered that one mechanism by which cytokines manipulate macrophage responses to Histoplasma is by altering the zinc/metallothionein axis. GM-CSF enhances the antifungal activity of macrophages by creating an intracellular environment that is deficient in zinc, and thus the fungus fails to survive. Interleukin-4, by contrast, increases zinc assimilation by the fungus, thus fortifying its resistance to the antimicrobial machinery of macrophages. Metallothioneins, which bind divalent cations such as zinc, are a key link to the availability of zinc in macrophages. The impact that the zinc/metallothionein axis exerts on host defenses to this pathogen will be discussed.
Wednesday, March 25, 2020 at 12:00 PM
2506 Veterinary Medicine Basic Sciences Building
2001 South Lincoln Avenue, Urbana
For more information contact the Department of Pathobiology at 217-333-2449, email firstname.lastname@example.org.