Evasion of adaptive immune defenses by the lethal chytrid fungus Batrachochytrium dendrobatidis

• Main Author: Fites, Jeffrey Scott
• Other Authors: Katherine Friedman
• Format: Others
• Language: en
• Published: VANDERBILT 2014
• Subjects: Biological Sciences
• Online Access: http://etd.library.vanderbilt.edu/available/etd-02252014-165554/

In the sixth mass extinction, amphibians are being lost in greater numbers than almost any other taxon. The deadly skin disease, chytridiomycosis, has taken a great toll on amphibian populations around the globe. Batrachochytrium dendrobatidis, the causative agent of chytridiomycosis, appears to have evolved as an obligate pathogen and thus must evade destruction by the amphibian defenses in order to reproduce. Several defenses along the skin mucosa likely inhibit the initial colonization by B. dendrobatidis zoospores, but B. dendrobatidis persists longer in the epithelium where it must survive any onslaught by innate and adaptive immune responses. Batrachochytrium dendrobatidis does this by evading phagocytes inside keratinocytes and impairing lymphocytes that might coordinate a robust immune response. Soluble molecules produced by B. dendrobatidis inhibited B and T cell proliferation and induced lymphocyte apoptosis. These molecules were only produced by cell-walled life-cycle stages that are present in host tissue. Inhibiting cell-wall biosynthesis with a chitin-synthase inhibitor greatly reduced its capacity to inhibit lymphocytes, suggesting that inhibitory factors are located in the cell wall. Treatments of inhibitory factors showed that the soluble molecules are not likely to be proteins or common structural components found in fungal cell walls. Although the B. dendrobatidis cell wall has not been characterized, fungal cell walls are largely composed of carbohydrate suggesting that inhibitory factors may be small molecules and/or carbohydrates. These data suggest that B. dendrobatidis has evolved a survival strategy targeting adaptive immune defenses in the skin of amphibian hosts.