The National Institutes of Health (NIH) has awarded Priya Uppuluri, PhD, investigator at The Lundquist Institute, and her team an R21 grant to investigate newly discovered immune pathways that protect against oropharyngeal candidiasis (OPC), a common and debilitating fungal infection in immunocompromised individuals.
OPC is caused by Candida albicans, a normally harmless oral commensal that can cause severe mucosal disease when host immunity is compromised. Despite antifungal therapy, OPC continues to cause significant morbidity in patients with cancer, HIV/AIDS, and other immune disorders.
The Uppuluri Lab recently identified an unexpected immunoregulatory dimension to mucosal antifungal defense. Using cutting-edge spatial transcriptomics (Visium 10X Genomics), the team discovered activation of the IL-33/ST2 signaling axis, M2 macrophages, and a family of epithelial-derived small proline-rich proteins (SPRRs) during infection.
Preclinical studies showed that recombinant IL-33 and SPRR proteins significantly reduced fungal burden in mouse models, with SPRRs demonstrating direct antifungal activity in vitro. These findings reveal previously unrecognized immunomodulatory and epithelial mechanisms that may complement traditional inflammatory pathways in controlling fungal infection.
“This award allows us to investigate an entirely new dimension of mucosal immunity,” said Dr. Uppuluri. “By understanding how epithelial signals and immune responses work together, we hope to identify safer and more effective approaches to treat fungal infections in vulnerable patients.”
This pioneering work aims to identify new therapeutic strategies that enhance host defense without exacerbating tissue damage.
Learn more about OPC in Dr. Uppuluri’s publication, “A spatial transcriptomic atlas of the host response to oropharyngeal candidiasis,” here: https://pubmed.ncbi.nlm.nih.gov/40586608/.