GSBSE Faculty Rob Wheeler Awarded Fulbright Grant for 2015-2016

Project Title: “Fungal-immune recognition dynamics during infection”

Project Summary: Infectious fungal disease is an important but underappreciated clinical problem worldwide (Brown et al., 2012). The innate immune system distinguishes self from non-self during infection on the basis of conserved microbial components (Lionakis and Netea, 2013; Netea et al., 2008). Our laboratory discovered that some fungal molecules crucial for immune recognition are normally hidden by the pathogen, only revealed by immune attack or a specific class of antifungal drugs (Wheeler and Fink, 2006; Wheeler et al., 2008). Our work has focused on tractable systems to identify the molecular mechanisms in fungi and in the host that mediate evasion and unmasking of one fungal-specific molecule, β-glucan. While recognition of this ligand plays an important role in immunity to some types of fungal infection in the mouse and human, there are other fungal components that dictate immune response (Lionakis and Netea, 2013; Netea et al., 2008). The relative contributions of different recognition pathways regulate the strength and tenor of immune response, modulating pathogen clearance and symptomatic inflammation. Thus, understanding dynamics of a number of fungal ligand-immune receptor interactions during infection can help to point out new ways to intervene and reduce the severity of fungal infection. In this project, we propose to examine clinical samples from human infections to test if similar dynamics occur in vivo. Combining our expertise in epitope unmasking with the clinical immunological expertise of the Vecchiarelli laboratory, we will use probes for host antibodies and soluble forms of immune receptors to quantify epitope availability on fungi during infection. Overall, we expect these experiments to expand our view of fungal infection dynamics to encompass changes in fungal epitope exposure during the course of their interactions with human cells. Our findings may eventually have translational impact by identifying pathways to target for enhanced immunity or control of symptomatic inflammation.

He will be in Perugia, Italy from January through June 2016.