The inaugural Mucosal Immunology Course and Symposium were held in Toronto (Canada) July 27-30, 2016, with specific focus on the microbiota and mucosal immunity in health and disease. The “Principles of Mucosal Immunology” course, held one day prior to the symposium, featured a full day of talks by experts in the field of mucosal immunology. The speakers provided a comprehensive overview of basic mucosal immunology that centered on how bidirectional interactions between the microbiota, epithelium and immune system are critical for determining health and disease. In particular, Greg Sonnenberg from Cornell Medical College (USA), reviewed the emerging role of innate lymphoid cells (ILCs) in the intestine and emphasized both their protective and tissue repair functions, as well as their contributions to inflammation and disease. While mouse models have provided valuable tools to study ILC populations and their heterogeneity, the need for human studies using standardized methods and controls was highlighted; these studies will allow for a better understanding of protective versus pathogenic cell populations and how we may selectively target these populations as therapies for inflammation-related diseases, such as inflammatory bowel disease (IBD).
The symposium that followed the course consisted of plenary sessions featuring experts on topics related to mucosal immunology as well as abstract sessions featuring trainees and rising stars. A number of sessions at the symposium highlighted the need to better understand the mechanisms by which microbiota contributes to disease. Often, we correlate changes in intestinal microbiota composition with changes in immunity and disease outcome. However, the need to prove causation was emphasized.
The use of animal models to demonstrate how host-microbe interactions can cause disease was an important take-home message from the symposium. Colonization of germ-free mice with microbiota from patients or healthy donors, or with specific bacterial communities, provide a means to tease out the contribution of microbial communities to immune responses, barrier function, and disease. For example, Christina Hayes, a PhD candidate from McMaster University (Canada), used mice colonized with human microbiota to demonstrate that commensal colonization and intestinal barrier maturation are closely linked. Moreover, decreased barrier integrity and systemic exposure to microbes early in the colonization process may increase susceptibility to mucosal injury; this highlights the importance of establishing intestinal homeostasis.
Translational approaches to study host-microbe interactions was another widely discussed topic at the symposium. Studies utilizing “humanized” mice (colonized with human microbiota) or mice expressing human genes, and studies utilizing human biopsies can aid in the translation from basic research to clinical studies.
Many speakers, including Elena Verdu from McMaster University and June Round from University of Utah (USA), highlighted the importance of understanding what initiates the excessive or inappropriate immune activation that leads to inflammatory diseases. While altered microbial composition has been suggested to be a key player in this, researchers do not know what exactly is dysregulated and there are inconsistent reports in the field. This highlights the need to characterize not only the composition of the microbiota, but also the functional properties of the microbiota in order to understand how microbes contribute to disease. As highlighted by Noah Palm from Yale University School of Medicine, different microbes from different taxa may demonstrate similar functions under certain conditions. This underscores the need to understand the functional changes in the microbiota that occur with environmental changes, how these are associated with disease genotypes, and what features of these functional profiles make them potentially disease modifying. In line with this, Alberto Caminero, a postdoctoral fellow from McMaster University, demonstrated that microbes in the small intestine can differentially influence host immune responses to the dietary protein gluten, the trigger for celiac disease, by participating in its degradation. While both opportunistic pathogens and commensals can digest gluten in the small intestine, certain opportunistic pathogens generate highly immunogenic peptides and resident Lactobacilli detoxify them. This represents a novel way to investigate how functional interactions between the microbiota and the diet contribute to autoimmune diseases.
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