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MEETING REPORT - The International Congress of Immunology (IUIS) in Cape Town, South Africa- by Javiera Villar

Meeting report by Javiera Villar who was awarded a travel grant by the CFCD
Javiera Villar was a PhD student working at Elodie Segura's laboratory at the Curie Institute, Paris France

The IUIS 2023 congress took place in Cape Town, South Africa, from 27th November to 2nd December 2023. The program was very dense, with up to 6 sessions in parallel and with several keynote lectures. I will next summarize some of the talks that I attended:

Opening Keytone Lecture : Vishva Dixit

Vishva Dixit (United States) in his talk ‘Why so many ways to die?’ showed how they discovered the mechanisms by which IL1B is released from immune cells. Briefly, they discovered Gasdermin D (GSDMD), which is cleaved by Caspase-1 and then form pores that allow IL1B release, acting as a perforator of the cells. In a second part, he showed unpublished data about interferon stimulated genes (ISGs) which expression is regulated independently of IFN type I signaling. Using BMDCs as model, the first observation was that IRF2 KO cells didn’t have a decreased ISG expression but ISGs expression was switched. He showed that these ISGs are actually regulated by an interplay between IRF1 and IRF2 and they do not dependent on IFNAR signaling.

Session “Tissue Macrophages in Health and Disease”

Firstly, Filip Swirski (United States) presented about ‘Lifestyle factor effects on brain-immune cell communication’. He talked about how sleep fragmentation affects hematopoiesis and monocyte differentiation from LCK progenitors. He also showed that sleep fragmentation triggers the growth of brain lymph nodes (CLNs). In the last part, he showed how restriction-induced stress induces neutrophilia and protection from infection.

Secondly, Carla Rothlin (United States) in her talk ‘TAMpering with memories’ described the role of disease associated macrophages (DAMs) in the progression of alzheimer. DAMs express Trem2, Spp1 and Axl. Axl is a damage sensor related with phagocytosis and anti-inflammatory signals. She showed how the knock down of AXL in microglia accelerates cognitive decline during a model of alzheimer. She mentioned that normally Axl is cleaved to decrease its activity as a regulation mechanism. So, they generated an Axl cleavage-resistant mouse model. During Alzheimer onset, these mice (with increased Axl activity) kept the ability to remember in a novel-object recognition test compared to wild type mice.

Finally, Steffen Jung (Israel) presented about monocyte-derived microglia. Their first observation was that the monocyte fate mapper model Ms4a3cre x RosatdTomato presented microglia that were tdTomato positive (microglia derived from monocytes, moMg). Transcriptomic analysis showed that these monocyte-derived microglia was identical to the classical yolk-sac derived microglia. Actually, Sall1 was thought to be a marker of microglia, however they observe that moMg also acquire Sall1 expression with time. He showed that moMg accumulate in some brain regions (except cortex) and they resemble bone fide yolk sac microglia.

Abstract session “Dendritic cell regulation of immune response”

Ghita Ghislat (London, United Kingdom) presented “NF-κB–dependent IRF1 activation programs cDC1 dendritic cells to drive antitumor immunity”. She showed that IRF1 KO possess decreased mature cDC1 cells in the tumor, and increased IFN-expressing dendritic cells that she calls ‘intermediate’ cDC1 (converting to the mature state). The knock-out of IkB, the inhibitor of NFkB, also has a decreased number of mature cDC1 in the tumor. She described that IRF1 KO deaccelerates the maturation of cDC1, which is downstream of NFkB signaling during cDC1 maturation, as NFkB inactivation decreases IRF1 expression.

Diana Dudziak (Jena, Germany) presented “Inflammasome responses and hyperactivation in human primary dendritic cell subpopulations”. She presented about how human dendritic cells react to inflammatory stimulation. Using in vitro culture of sorted cells, she showed that cDC2 stimulated with TLR ligands secrete IL1B upon inflammasome activation, which normally leads to pyroptosis. However, cDC2 do not die. This phenomenon was described in 2020 by Zhivaki et al., Cell Reports, and it is called ‘hyperactivation’ as there is a slow release of IL1B that doesn’t trigger pyroptosis. She also showed that cDC2 actually behave differently to DC3 upon TLR stimulation: cDC2s undergo hyperactivation (slow release of IL1B without cell death), while DC3 secrete high amounts of IL1B which leads to pyroptosis.

Plenary Lectures “Fibrosis and Type 2 Immunity in Health and Disease”

Bart Lambrecht (Belgium) presented about ‘Spontaneous protein crystallization as a driver of immunity’. During asthma the airways are narrowed which is accompanied by a mucus plug. This mucus contains crystals. Bart Lambrecht showed us that it is the eosinophils who secrete galectin-10 in the airways, and galectin-10 forms this charcot-leyden crystals. Neutrophils will detect crystals and secrete DNA (to form neutrophil extracellular traps, NETs). By analyzing the structure of Gal-10 crystals by X-ray crystallography, they observed that Gal-10 crystals have a pocket that binds DNA, creating a sort of interlacing of crystals and making the mucus stiffer. He spoke about how they developed antibodies that are able to dissolve these crystals. Regarding the analogous mechanism in mice, as they don’t have galectin-10, he mentioned that proteins as Chil3, Chil4 and Ym1/2 (chitinase-like proteins) sustain mucus production in mouse.

Finally, I would like to thank the CFCD for their financial support to assist this amazing congress. I had the chance to present for the first time the last work from my PhD and to discover a widely variety of topics in immunology.