Diverse fungal community (the mycobiome) colonizes all barrier surfaces of the body. While some commensal fungi can be opportunistic pathogens and can lead to serious infections upon a bridge of the mucosal barriers, evidence coming from the Iliev Laboratory suggests that a balanced fungal community is necessary for the maintenance of intestinal health.
The Iliev Laboratory is specifically interested in molecular mechanisms by which fungi interact with gut-resident phagocytes to drive protective or inflammatory immunity. Using in vivo murine models lacking immune arms and antifungal receptors, we study the interaction of commensal fungi with the gut immune system during steady state and during inflammatory states. Our final goal is to understand how this interaction is regulated and provide strategies to manipulate these pathways.
CX3CR1+ mononuclear phagocytes (green) in the intestinal villi (blue) uptake Candida albicans (red).
Fungal and bacterial communities share similar niches in the intestine where they interact and co-depend on each other. Using murine models of intestinal inflammation and samples from patients with inflammatory bowel disease, the Iliev Lab aims to understand the interconnection between gut fungal and bacterial communities. We study how changes in bacterial communities will affect the fungal counterpart of the intestinal microbiota and whether bacteria can respond to changes in the mycobiota. The lab utilizes a combination of approaches to promote microbiota instability in vivo and to track pathways important for the interaction between fungi and bacteria. We aim to address a fundamental question about how eukaryotic and prokaryotic microbes interact in the intestine.
Commensal fungi (green) cohabitate with commensal bacteria (red) in the mouse gut
Inflammatory bowel disease (IBD) is a multifactorial disease, driven by a combination of genetic and environmental factors leading to immune responses against the host own microbiota. We have recently shown that innate immune deficiency targeting the CX3CR1+ mononuclear phagocytes predisposes mice to intestinal inflammation triggered by gut fungi. We found that a loss of function mutation in the gene encoding for CX3CR1, is strongly associated with a decrease of antifungal antibody responses in Crohn’s Disease patients (a form of IBD). Recent clinical and experimental studies suggest that fungal microbiota (mycobiota) composition dramatically changes in the course of the intestinal inflammation. We apply microbiota transplantation, microbiota modification with drugs and several murine models of intestinal inflammation to assess the role of the gut mycobiota in disease development and progression.