From June 6-9, immunologists across the country gathered in the charming Eastern township of Orford, Quebec for the 35th annual meeting of the Canadian Society for Immunology (CSI) at the Hôtel Chéribourg. While the rainy weather dissuaded most from exploring the scenic trails around the conference site, the beautiful scenery nonetheless acted as a welcoming backdrop to four days of exciting immunology and networking with our colleagues from coast-to-coast.
KEYNOTE
CSI 2023 opened with a keynote address delivered by Dr Luke O’Neill (Trinity College Dublin), showcasing how lessons learned from rare human diseases can help us better understand the underlying immunology for broader therapeutic applications. Thematic to this issue of IMMpress Magazine, the unifying concept of this address was how mitochondrial dysfunction underpins many flavours of inflammatory and autoimmune diseases. Poised at the intersection of biochemistry and immunology, Dr O’Neill spoke on the role of two Krebs’ cycle intermediates, itaconate and fumarate – molecules generated in the mitochondria during the process of metabolic respiration – in both metabolism and modulating the immune response. Macrophages stimulated by lipopolysaccharides (LPS), a major bacterial toxin, upregulate both itaconate and fumarate. Dr O’Neill and his team demonstrated that itaconate and related derivatives inhibit proteins involved in inflammatory pathways such as NLRP3 and JAK1, leading to anti-inflammatory and anti-microbial effects. On the other hand, fumarate accumulation, which occurs through fumarate hydrogenase inhibition, drives type I interferon release via mitochondrial stress and induced inflammatory responses. Interestingly, fumarate dehydrogenase has been found to be repressed in lupus patients, implying a role for metabolic dysregulation in certain autoinflammatory diseases. The stories of these two metabolites emphasized the untapped potential of immunometabolites as both therapeutic targets and agents across a spectrum of immune-mediated diseases.
PERSONALIZED IMMUNITY
The first symposium explored how different biological aspects can be considered to tailor therapies for effective clinical outcomes. Dr Ivona Aksentijevich (National Human Genome Research Institute) discussed how patient stratification by molecular diagnosis is critical in informing targeted therapies, particularly in cases of autoinflammatory diseases. Next, Dr Keke Fairfax (University of Utah) spoke on how helminth infection by Schistosoma mansoni can interact with biological sex to modulate the risk of developing metabolic syndromes, conferring protection against atherosclerosis, obesity, and diabetes in male, but not female, mice. Dr Naoto Hirano (University of Toronto) then brought us to the other end of the spectrum of personalized medicine, introducing the generation of an HLA-agnostic chimeric antigen receptor (CAR) T cell therapy against the tumour antigen WT1 that can bypass the issue of cell therapy-patient HLA class II incompatibility. Dr Channakeshava Umeshappa (Dalhousie University) described a novel peptide-MHCII nanomedicine strategy that induces the differentiation of a novel regulator Maf+LiNKTR1 invariant natural killer T cell population that may represent a potential therapy in autoimmune liver diseases. Concluding the first symposium, Dr Marc Horwitz (University of British Columbia) demonstrated that latent chronic Epstein-Barr virus infection can drive increased susceptibility and severity of multiple sclerosis (MS) in mice, and discussed how this approach can be adapted using human immune cells to create personalized preclinical models of MS for therapeutic testing.
MECHANOSENSING
Kicking off the second full conference day was a series of talks on how cell migration can influence immune function. Dr Morgan Huse (Memorial Sloan Kettering Cancer Center) showed how biophysical characteristics like plasma membrane abundance link the processes of phagocytosis and migration, providing evidence that deficiencies in the G protein subunit Gβ4 lead to altered patterns of chemotaxis and phagocytosis in myeloid cells. Moving towards the field of cancer immunology, Dr Valerie Weaver (University of California, San Francisco) described how fibrosis and stiffening of the tissue in breast cancer can be sensed by tumour cells to drive the epithelial-mesenchymal transition (EMT) and promote tumour metastasis. Dr Pablo Vargas (French Institute of Health and Medical Research) brought with him astonishing videos of various immune cells in motion as they maneuver through micro-fabricated obstacles and confined spaces reminiscent of the anatomical landscapes they scale daily while patrolling our tissues. Dr Judith Mandl (McGill University), the co-chair of this symposium, then took the stage to discuss how mechano-sensing of the tissue environment can act as a cue for tissue-resident memory T cell differentiation, initiated through changes in cellular cytoskeletal components such as F-actin. Rounding out the second symposium was Dr Spencer Freeman (University of Toronto), who spoke on how internal mechanical stresses within macrophages during fluid handling can translate into inflammatory responses.
THROMBOINFLAMMATION
The last symposium brought focus to an oft-overlooked cell type that straddles the fields of immunology and hematology – platelets. Dr Bryan Heit (University of Western Ontario) shared his observations on the potential link between platelet activation and increased thrombotic events in patients infected with influenza A virus, which may be driven by the elevated levels of platelet-derived microvesicles enriched with transmembrane tissue factor in the serum of these patients. Continuing the discussion on the role of platelets in respiratory infections, Dr Milka Koupenova (University of Massachusetts Medical School) explained how platelets can initiate innate immune responses against respiratory viruses, such as influenza and SARS-CoV-2, by internalizing the virus and activating immune cells via complement and exosome release. Despite the ability of platelets to initiate an inflammatory response, Dr Julie Rayes (University of Birmingham) spoke about how the immune functions of platelets are resistant to classic anti-platelet therapies in the context of inflammation, highlighting neutrophils as a central regulator for platelet activation through the release of danger-associated molecular patterns (DAMPs) that promote thrombosis and further leukocyte recruitment and activation. Dr Genevieve Pepin (Université du Québec à Montréal) took a step back to examine platelet development, which could provide clues to how platelet-intrinsic mechanisms through the cGAS/STING pathway may drive thromboinflammation. As the final symposium speaker for this year’s meeting, Dr Patricia Liaw (McMaster University) described how neutrophils activate coagulation through NETosis – the release of DNA to trap and contain extracellular pathogens – in sepsis patients. Tying in themes from the first symposium on personalized immunity, Dr Liaw highlighted two biomarkers, the levels of circulating DNA and coagulant protein C, in stratifying sepsis patients for treatment based on the pathological contribution of neutrophils versus thrombosis.
AWARDS AND ACKNOWLEDGEMENTS
Our congratulations to Dr Zhou Xing (McMaster University), the recipient of this year’s Bernhard Cinader Award. He shared with us his work on the effectiveness of inhaled vaccines in boosting the local respiratory immune response following a primary intramuscular vaccine, such as in the case of tuberculosis and COVID-19. Dr Xing highlighted the ability of this vaccine strategy in inducing a tripartite immune protection involving T cells, B cells, and lung macrophages, and provided two examples of such vaccines developed by his lab currently in clinical trials. He left us with some insights as a “solitary scientist” amidst the academic social scene, encouraging introverts among the room to “unleash the quiet power in an ever louder scientific world”. Other awardees of the year included Dr Kelly McNagny (University of British Columbia), recipient of the Investigator Award, and Dr Daniela Quail (McGill University), recipient of the New Investigator Award. A warm round of congratulations also goes out to all travel and poster award winners.
We were saddened this past year to have lost two long-standing members of the CSI community, Dr John Bienenstock (McMaster University) and Dr James Carlyle (University of Toronto), and in memoriam speeches were prepared by friends and colleagues to honour their contributions.
The CSI 2023 meeting would not be made possible without the generous support from an impressive list of sponsors: BioLegend (Champion Sponsor), 10X Genomics, Miltenyi Biotec, Thermo Fisher, Cytek Biosciences, Sony Biotechnology, CIHR, Clinical Immunology Network – Canada, Biogen Canada, Université Laval, Cedarlane Laboratories, Centre de recherche de l’Hôpital Maisonneuve-Rosemont, CHU Ste-Justine, CIHR – Institute of Infection and Immunity, Université de Sherbrooke, Leinco Technologies, Paraza Pharma, Centre for Research of the CHUS, and Université du Québec à Trois-Rivières.
Last but not least, we thank the local organizing committee, the Trainee Engagement Committee, and staff for their tremendous work in putting together a packed schedule of talks, workshops, and trainee events: Dr Manu Rangachari (Chair – Université Laval), Dr Hélène Decaluwe (CHU Ste-Justine), Dr Momar Ndao (McGill University), Dr Martin Pelletier (Université Laval), Dr Geneviève Pépin (Université de Quebec à Trois-Rivières), and Dr Lee-Hwa Tai (Université Sherbrooke). Congratulations on a successful conference, and we look forward to seeing everyone again next year in Banff, Alberta for the 36th CSI meeting!
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