Fungi are normal members of the human gut microbiome that rarely cause disease and may even induce beneficial immune responses that promote immune surveillance. However, these fungi have significant pathogenic potential; the Candida species dominating the gut fungal community are notorious opportunistic pathogens capable of causing life-threatening disseminated infections. Candida species can also drive pathogenic inflammation in the gut and are associated with worsened inflammatory bowel disease in people. It is still largely a mystery as to how these fungi reside peacefully in the gut of most people. The goal of the Ost lab is to uncover the biological forces that constrain these fungi to a commensal state to prevent disease. We recently discovered that adaptive immunity is critical for maintaining the peace with commensal Candida and interestingly, does so in a way that mutually benefits host and fungus. IgA antibody targeting of Candida both reduces its pathogenic potential during colitis, while also improving its fitness for colonizing the gut. We also found that vaccination could be used to restore homeostasis with Candida albicans. Our lab works to uncover the immune and fungal pathways regulating homeostasis by combining mouse models of fungal colonization and inflammatory bowel disease with powerful Candida molecular genetic tools. This work is largely focused on three main areas.
- Define the function of IgA-targeted fungal effectors in regulating host and fungal homeostasis in the gut. We are using different Candida mutant strains or clinical isolates in combination with mouse colonization and disease models to understand how specific fungal pathways impact the induction of intestinal IgA/B cell/T cell responses and their role in colitis.
- Investigate how intestinal adaptive immune responses regulate fungal biology. We found that the adaptive immune environment shapes the transcriptional profile of commensal Candida albicans in the gut. We are working to identify the immune pathways and mechanisms involved in this sculpting.
- Explore vaccination strategies aimed at promoting homeostasis with fungal commensals. We recently found that a clinically relevant anti-Candida vaccine blocks Candida albicans from exacerbating a mouse model of colitis. We are investigating the immune mechanisms behind this protection and exploring additional vaccine targets aimed at reducing the pathogenic potential of Candida in the gut.
Click here for a list of Dr. Ost’s recent publications
