The mammalian gastrointestinal tract is colonized by diverse commensal microbial communities consisting of bacteria, fungi and viruses. The Iliev Laboratoty laboratory studies the interaction between this commensal microbiota and the immune cells at the mucosal surfaces of the body. Our research is specifically focused on understanding the functional consequences of fungal microbiota (mycobiota) composition and metabolism to the host's immunity and to bacterial populations in the gut. In this effort, we have developed in vivo models, model fungal strains and bioinformatics pipelines that aid with tools to study the role of gut fungi in mucosal immunity during health and during conditions, such as inflammatory bowel disease, allergy and immunosuppression, in which fungi can contribute to pathologies.
Immunity to Mucosa-Associated Fungi
Diverse fungal communities colonize all mucosal 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 lab 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 and polarize protective adaptive immune responses. 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 colitis. Our final goal is to understand how this interaction is regulated and provide strategies to manipulate these pathways.
Characterization of Intestinal Fungal Communities (Mycobiota) and Their Interaction with Bacteria
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 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.
Gut mycobiota and inflammation
Inflammatory bowel disease (IBD) is a complex disease, driven by a combination of genetic and environmental factors leading to immune responses against a host’s own microbiota. We have recently shown that innate immune deficiency in the antifungal receptor Dectin-1 predisposes murine models to intestinal inflammation triggered by gut fungi. A polymorphism of CLEC7a, the gene encoding for Dectin-1, predisposes patients to severe ulcerative colitis (a form of IBD). Recent clinical and experimental studies suggest that microbiota composition dramatically changes in the course of the intestinal inflammation. We apply microbiota transplantation, microbiota depletion and a few murine models of intestinal inflammation to assess the role of the gut mycobiota in disease development and progression. Bacterial and fungal changes during the course of disease are analyzed by 16S and ITS1 deep sequencing approaches and microbiota analysis platforms.
Iliyan Iliev earned his PhD from the European School of Molecular Medicine and the University of Milan in Italy. He has completed research training at Tohoku University in Japan, the European Molecular Biology Organization in Germany and the European Institute of Oncology in Italy.
Iliev ID, Dectin-1 Exerts Dual Control in the Gut. Cell Host & Microbe (2015) 12;18(2):139-41.
Tang J*, Iliev ID*, Brown J, Underhill DM*, Funari VA*. Mycobiome: Approaches to Analysis of Intestinal Fungi. Journal of Immunological Methods (2015); 421:112-21. * These authors contributed equally to this work
Seehus CR, Aliahmad P, de la Torre B, Iliev ID, Spurka L, Funari VA, Kaye J., The development of innate lymphoid cells requires TOX-dependent generation of a common innate lymphoid cell progenitor. Nat Immunol. (2015); 16(6):599-608.
Underhill DM and Iliev ID, The mycobiota: interactions between commensal fungi and the host immune system. Nature Reviews Immunology (2014), 14, 405–416. http://www.ncbi.nlm.nih.gov/pubmed/24854590
Iliev ID and Underhill DM, Striking a balance: fungal commensalism versus pathogenesis. Current Opinion in Microbiology (2013) 1369-5274(13)00071-4.
Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DPB, Brown GD, Underhill DM, Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science (2012) 8;336(6086):1314-7.
Iliev ID, Spadoni I, Mileti E, Matteoli G, Sonzogni A, Sampietro GM, Foschi D, Caprioli F, Viale G, Rescigno M., Human intestinal epithelial cells promote the differentiation of tolerogenic dendritic cells, Gut (2009) 58(11):1481-9
Iliev ID, Mileti E., Matteoli G, Chieppa M., and Rescigno M., Intestinal epithelial cells promote colitis-protective regulatory T cell differentiation through dendritic cell conditioning, Mucosal Immunol. (2009) 2(4):340-50
Iliev ID, Matteoli G and Rescigno M., The yin and yang of intestinal epithelial cells in controlling dendritic cell function, J Exp Med. (2007), 204(10):2253-7
Iliev ID, Kitazawa H., Shimosato T., Katoh S., Morita H., He F., Hosoda M. , Saito T., Strong immunostimulation in murine immune cells by Lactobacillus rhamnosus GG DNA containing novel oligodeoxynucleotide pattern, Cellular Microbiology
(2005), 7(3): 403-414