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Meeting report : DC2018

Meeting report from Camille Wagner, recipient of a CFCD travel award

The 15th International Symposium on dendritic cells (DC) was held at the border of Belgium and the Netherlands in Aachen, Germany. This symposium aims to connect researchers from around the world interested in the comprehension of DC biology in health and disease. This year edition covered a wide variety of topics: from the use of omics approaches to unravel DC heterogeneity to DC functions, such as antigen processing and crosstalk with T cells. Two workshops were dedicated to deciphering DC development and ontogeny on a molecular level. The role of DC in infectious settings, in cancer and their interaction with commensal microbiota were also largely discussed.
The keynote lecture given by Bart Lambrecht (Ghent, Belgium) has driven a lot of attention. His team focuses on lung DC in airways chronic inflammatory diseases such as asthma and viral infection. He presented interesting unpublished data regarding airways DC in response to allergens.
During an allergy, epithelial cells release cytokines and danger signals, thus activating the innate immune system. However, the precise mechanisms of how airways epithelial cells activate innate cells and how it mediates Th2 response remain elusive. Allergy is characterized by expression of type 2 immunity inflammatory cytokines by eosinophils. The latter are specialized in killing large extracellular parasites by secreting harmful compounds. This induces many damages to the tissue. One of these compounds is Galectin-10, which represents 10% of human eosinophils granule contents. Galectin-10 form crystals, also called Charcot-Leyden proteins. Uric acid crystals are already known to induce Th2 response, but could Galectin-10 crystal be pathogenic as well? Crystallography analysis of Galectin-10 reveals its dimeric structure, further associating in tetramer to form crystal. Using mutated version of Galectin-10, it is possible to study soluble or other crystal forms of the protein. In vivo in a mice model, the soluble form failed to induce eosinophils recruitment and pro-inflammatory cytokines production. Moreover, using the antigen specific T cell model OTII, only the crystal form of Galectin-10 was able to induce T cells proliferation and a specific IgG immune response. However, Galectin-10 is not express in mice. Could the immune response happen in this model only because it is a neo-antigen? To test this hypothesis, they used transgenic mice where eosinophils expressed human Galectin-10. The constitutive expression of Galectin-10 activates the immune system in a similar fashion, with a specific humoral response. Finally, they designed antibodies specific for the crystal form of Galectin-10 by vaccinating llama. They very nicely demonstrate its efficacy ex vivo in a video: they took mucus of patients with asthma, and crystals are easily seen. When adding the specific antibodies, we could see crystals “dissolving” and disappearing. Anti-Galectin-10 Fab portions mimic the protein-protein bond of dimeric Galectin-10 and thus break this bond by competition. This impressive work has unraveled Galectin-10 structure and its role in inducing immune response. The use of specific antibodies to dissolve these crystals leads to potential new therapeutic approaches against asthma and airways allergy, which are crucially needed today.
I was also very interested in Leif Sander (Berlin, Germany) lecture. His team works on infectious diseases and vaccinology; here, he presented their latest publications on mechanisms and consequences of sensing microbial viability.
Bacterial infection can be avoided with efficient vaccines. Unfortunately, in the past decade, we witnessed an increase in multidrug resistance, leading to re-emerging infections. Today, we still do not know the underlying mechanisms leading to most of efficient vaccines. His team demonstrated in 2011 that mice antigen-presenting cells are able to differentiate between live and dead bacteria via the detection of prokaryotic mRNA. In their latest publication, they study how this mechanism works in human cells. In vitro, human monocytes-derived DC stimulated with live attenuated Escherichia coli, but not heat-killed E. coli, were able to polarize naïve T cells in T follicular helper cells. This detection by DC was dependent on TLR8 and the polarization was dependent on secretion of IL12p40 by DC. When co-cultured with B cells, these TFH are able to induce their differentiation to IgG secreting
plasma cells. They reproduce their experiments on swine, which also have a functional TLR8, using the live Salmonella enterica Thyphimurium vaccine or the heat-killed bacteria, and obtain similar results. In vivo, swine vaccination with live S. enterica Thyphimurium, but not the heat-killed bacteria, leads to a humoral immune response. Thus, recognition of live bacteria for the induction of TFH and an efficient humoral response is conserved between human and swine. Moreover, TLR8 recognition of live pathogens is important for this efficient antibody response. Thus, the work of Leif Sander team bring new insight on vaccine designing.
Overall, this symposium was a great opportunity to learn on latest research on DC biology in multiple contexts, provided by experts in their field. It was also an opportunity to meet, discuss, and exchange with researchers, to further move science forward as a community.