Meeting report from Molène Docq, recipient of a CFCD travel award.
Molène is a PhD student at the Université Paris-Saclay in the research team INSERM UMR 996 "Inflammation, Microbiome et Immunosurveillance"
During this 3-day joint congress of the French Society for Immunology (SFI) and the French Cytometry Association (AFC) that took place in Nice, France, from the 22th to the 24th of November in 2022, a wide range of scientific conferences and poster presentations covering fundamental, clinical and technological aspects of Immunology and Cytometry were presented.
The program was dense and varied with topics covering immune cells (e.g. innate lymphoid cells, mast cells, T cells, dendritic cells (DCs)), their environment, immunometabolism, immune aging, osteoimmunology, neuroimmunology, host/pathogen interactions, transplant immunology, immunotherapy, immuno-oncology, auto-immunity, and allergy. In addition, we had presentations on microbiota, microbiology, and even oceanobiology. Technical advances were also displayed about cytometry, high-content imaging, data analysis, omics, and multiparametric analysis.
Here, I attempt to summarize the presentations that particularly caught my attention.
Firstly, Yasmine Belkaid (National Institute of Allergy and Infectious Diseases, Bethesda, USA) introduced the congress with a great talk on the control of host immunity by the microbiome and the hormonal regulation of tissue immunity. She explained that females have stronger responses to skin commensals than males and that male sex hormones regulate immune responses to the microbiota. She presented data showing that there is a higher number of DCs in female’s skin than male’s and that female’s skin DCs are more activated. Moreover, she explained that in female’s skin there is a large population of ILC2 whose GM-CSF sustains the skin DC network while in male’s there are fewer ILC2, and thus less ILC2-derived GM-CSF with fewer DCs.
During the “Myeloid cells” session, Ignacio Cebrian (Centre for Genomic Regulation (CRG), Barcelona, Spain) presented new insights about the intracellular transport of MHC/peptide complexes. Indeed, the last steps that control the efficient transport of these complexes from the endocytic system to the plasma membrane remain poorly understood. Using bone marrow-derived DCs (BMDCs) from WT and GRASP55-/-C57BL/6 mice, his team found that both cross-presentation and MHC-II-associated antigen presentation are significantly inhibited in GRASP55-deficient DCs. Moreover, they observed that GRASP55 is recruited to late DC phagosomes, and that this recruitment is crucial for the efficient sorting of loaded MHC-I and II molecules from DC phagosomes to the plasma membrane.
Despoina Koumantou (INSERM, Paris) presented a new mechanism mediating the inducible cross-presentation capacity of type 2 DCs and inflammatory DCs (iDCs). Indeed, it was unclear whether it proceeds via the same mechanism as the one used in type 1 DCs, which are the most efficient cross-presenting DC subsets. It is known that FcγR-mediated uptake by DCs subsets mediates antibody-dependent cross-presentation and the activation of CD8+ T cell responses. Her team has shown that FcγR-mediated uptake triggers efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs. They demonstrated that FcγR-mediated cross-presentation on type 2 and iDCs rely on the enzymatic activity of p84/p110γ complex of PI3Kγ, which controls the activity of NADPH oxidase NOX2 and ROS production in murine splenic type 2 DCs and GM-CSF-derived iDCs. Thus, their findings lead to reconsidering the combination of anti-tumor monoclonal antibodies and PI3Kγ inhibitors in clinical practice.
Raquel Sal Carro (Strasbourg University, Strasbourg) gave results on the role of autophagy on the regulation of lipid metabolism and long-term survival of Langerhans cells (LCs) as, to date, no study had addressed the role of autophagy in LCs before. They generated Atg5DCd207 and Atg7DCd207 mouse models, where CD207+ LCs become autophagy-deficient through the deletion of Atg5 or Atg7 and found that autophagy-deficient LCs were gradually depleted from the epidermis and presented deregulated lipid metabolic pathways. Indeed, Atg5-deficient LCs accumulated neutral lipid droplets, which eventually led to the accumulation of toxic lipidic reactive oxygen species and ferroptosis. Then, she explained that LC ablation resulted in the upregulation of pro-inflammatory transcripts and decreased the innervation of the epidermis. To conclude, they found that the epidermal maintenance of LCs relies on autophagy-regulated lipid metabolism.
During the session “Hematopoiesis”, Tsvee Lapidot (Weizmann Institute, Rehovot, Israel) showed in a great talk that hematopoietic stem cells and progenitor cells (HSPCs) and host immunity are regulated in a circadian manner by light and darkness cues. These cues induce a fraction of bone marrow (BM) HSPCs to differentiate and egress from the BM in daylight to replenish the circulation with mature blood and immune cells while darkness metabolically elevates their self-renewal to maintain the BM reservoir of undifferentiated HSPCs. Using single stem cell RNA sequencing and flow cytometry with functional HSPC assays, they reported night long-term HSCs (LT- HSCs) to have lower mitochondrial membrane potential, previously associated with increased LT-HSC competitive repopulation potential. He explained that darkness cues are associated with enhanced hypoxia and enhanced transcriptional expression of glycolytic pathway genes.
In an interesting talk, Marlene Dreux (Université Claude Bernard Lyon 1, Lyon) explained that severe COVID-19 patients have impaired plasmacytoid dendritic cell (pDC)-mediated control of SARS-CoV-2-infected cells. They demonstrated that pDCs are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells and that, mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. She explained that, in turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, they further demonstrated that the pDC response is particularly impaired in severe COVID-19 patients. Overall, she proposed that pDC activation is essential to control SARS-CoV-2-infection.
In the session “Neuroimmunology” Sophie Ugolini (INSERM, Marseille) talked about the neuroimmune interactions in the skin. Indeed, during an inflammation, nociceptive sensory neurons release several mediators directly at the site of injury, modulating local immune responses. Sophie Ugolini and her team recently demonstrated a key role for subsets of sensory neurons in limiting inflammation and promoting macrophage tissue-repair functions in the skin. She explained that the sensory nervous system also regulates the adaptive immune response to Herpes simplex virus type 1 infection. Her team is currently exploring the molecular and cellular basis of these neuro-immune regulations and the potential therapeutic value of their findings for the treatment of inflammatory diseases.
During the “High content imaging” session, Laura Kuett (University of Zurich, Switzerland) presented a new workflow of 3D imaging mass cytometry for cell-level mapping of tissues. She explained their experimental workflow based on thin sectioning of samples together with computational image analysis steps for image registration and segmentation to achieve single cell level 3D imaging mass cytometry models. By applying this workflow and underscoring advantage of this method on different breast cancer samples she revealed how it could be applied to studying tumor microenvironment and metastasis-associated events. These models capture the phenotypic complexity of breast tumors by enabling simultaneous mapping of tumor, immune and stromal cells in tissue volumes and reveal spatial interactions that can be elusive on 2D images.
Paulina Garcia Gonzalez (Centre d’Immunologie de Marseille-Luminy/ CNRS/ Aix-Marseille Université, Marseille) presented a new method they developed to assess metabolic state, epigenetics, and immune profiling at a single cell level of immune cells. Using a small amount of sample, they were able to determine the functional metabolic status of lymphocytes, B cells, DCs, monocytes, NK cells, neutrophils, and basophils in peripheral blood with high resolution. They also efficiently measured histone modification marks in parallel, without altering their puromycin reading, thus obtaining a single-cell readout of metabolism and epigenetic heterogeneity at the same time. Interestingly, each immune cell type analyzed displayed a distinctive pattern of histone modification as well as a particular metabolic profile.
Finally, I warmly thank the CFCD for their financial support that gave me the opportunity to participate in this congress. It was a great experience that allowed me to present my data during the poster sessions and discover many aspects of Immunology that I did not know.
Molène is a PhD student at the Université Paris-Saclay in the research team INSERM UMR 996 "Inflammation, Microbiome et Immunosurveillance"
During this 3-day joint congress of the French Society for Immunology (SFI) and the French Cytometry Association (AFC) that took place in Nice, France, from the 22th to the 24th of November in 2022, a wide range of scientific conferences and poster presentations covering fundamental, clinical and technological aspects of Immunology and Cytometry were presented.
The program was dense and varied with topics covering immune cells (e.g. innate lymphoid cells, mast cells, T cells, dendritic cells (DCs)), their environment, immunometabolism, immune aging, osteoimmunology, neuroimmunology, host/pathogen interactions, transplant immunology, immunotherapy, immuno-oncology, auto-immunity, and allergy. In addition, we had presentations on microbiota, microbiology, and even oceanobiology. Technical advances were also displayed about cytometry, high-content imaging, data analysis, omics, and multiparametric analysis.
Here, I attempt to summarize the presentations that particularly caught my attention.
Firstly, Yasmine Belkaid (National Institute of Allergy and Infectious Diseases, Bethesda, USA) introduced the congress with a great talk on the control of host immunity by the microbiome and the hormonal regulation of tissue immunity. She explained that females have stronger responses to skin commensals than males and that male sex hormones regulate immune responses to the microbiota. She presented data showing that there is a higher number of DCs in female’s skin than male’s and that female’s skin DCs are more activated. Moreover, she explained that in female’s skin there is a large population of ILC2 whose GM-CSF sustains the skin DC network while in male’s there are fewer ILC2, and thus less ILC2-derived GM-CSF with fewer DCs.
During the “Myeloid cells” session, Ignacio Cebrian (Centre for Genomic Regulation (CRG), Barcelona, Spain) presented new insights about the intracellular transport of MHC/peptide complexes. Indeed, the last steps that control the efficient transport of these complexes from the endocytic system to the plasma membrane remain poorly understood. Using bone marrow-derived DCs (BMDCs) from WT and GRASP55-/-C57BL/6 mice, his team found that both cross-presentation and MHC-II-associated antigen presentation are significantly inhibited in GRASP55-deficient DCs. Moreover, they observed that GRASP55 is recruited to late DC phagosomes, and that this recruitment is crucial for the efficient sorting of loaded MHC-I and II molecules from DC phagosomes to the plasma membrane.
Despoina Koumantou (INSERM, Paris) presented a new mechanism mediating the inducible cross-presentation capacity of type 2 DCs and inflammatory DCs (iDCs). Indeed, it was unclear whether it proceeds via the same mechanism as the one used in type 1 DCs, which are the most efficient cross-presenting DC subsets. It is known that FcγR-mediated uptake by DCs subsets mediates antibody-dependent cross-presentation and the activation of CD8+ T cell responses. Her team has shown that FcγR-mediated uptake triggers efficient cross-presentation of exogenous antigens in otherwise inefficient cross-presenting cells, such as type 2 DCs and GM-CSF-derived iDCs. They demonstrated that FcγR-mediated cross-presentation on type 2 and iDCs rely on the enzymatic activity of p84/p110γ complex of PI3Kγ, which controls the activity of NADPH oxidase NOX2 and ROS production in murine splenic type 2 DCs and GM-CSF-derived iDCs. Thus, their findings lead to reconsidering the combination of anti-tumor monoclonal antibodies and PI3Kγ inhibitors in clinical practice.
Raquel Sal Carro (Strasbourg University, Strasbourg) gave results on the role of autophagy on the regulation of lipid metabolism and long-term survival of Langerhans cells (LCs) as, to date, no study had addressed the role of autophagy in LCs before. They generated Atg5DCd207 and Atg7DCd207 mouse models, where CD207+ LCs become autophagy-deficient through the deletion of Atg5 or Atg7 and found that autophagy-deficient LCs were gradually depleted from the epidermis and presented deregulated lipid metabolic pathways. Indeed, Atg5-deficient LCs accumulated neutral lipid droplets, which eventually led to the accumulation of toxic lipidic reactive oxygen species and ferroptosis. Then, she explained that LC ablation resulted in the upregulation of pro-inflammatory transcripts and decreased the innervation of the epidermis. To conclude, they found that the epidermal maintenance of LCs relies on autophagy-regulated lipid metabolism.
During the session “Hematopoiesis”, Tsvee Lapidot (Weizmann Institute, Rehovot, Israel) showed in a great talk that hematopoietic stem cells and progenitor cells (HSPCs) and host immunity are regulated in a circadian manner by light and darkness cues. These cues induce a fraction of bone marrow (BM) HSPCs to differentiate and egress from the BM in daylight to replenish the circulation with mature blood and immune cells while darkness metabolically elevates their self-renewal to maintain the BM reservoir of undifferentiated HSPCs. Using single stem cell RNA sequencing and flow cytometry with functional HSPC assays, they reported night long-term HSCs (LT- HSCs) to have lower mitochondrial membrane potential, previously associated with increased LT-HSC competitive repopulation potential. He explained that darkness cues are associated with enhanced hypoxia and enhanced transcriptional expression of glycolytic pathway genes.
In an interesting talk, Marlene Dreux (Université Claude Bernard Lyon 1, Lyon) explained that severe COVID-19 patients have impaired plasmacytoid dendritic cell (pDC)-mediated control of SARS-CoV-2-infected cells. They demonstrated that pDCs are the predominant IFN-I/λ source following their sensing of SARS-CoV-2-infected cells and that, mechanistically, this short-range sensing by pDCs requires sustained integrin-mediated cell adhesion with infected cells. She explained that, in turn, pDCs restrict viral spread by an IFN-I/λ response directed toward SARS-CoV-2-infected cells. This specialized function enables pDCs to efficiently turn off viral replication, likely via a local response at the contact site with infected cells. By exploring the pDC response in SARS-CoV-2 patients, they further demonstrated that the pDC response is particularly impaired in severe COVID-19 patients. Overall, she proposed that pDC activation is essential to control SARS-CoV-2-infection.
In the session “Neuroimmunology” Sophie Ugolini (INSERM, Marseille) talked about the neuroimmune interactions in the skin. Indeed, during an inflammation, nociceptive sensory neurons release several mediators directly at the site of injury, modulating local immune responses. Sophie Ugolini and her team recently demonstrated a key role for subsets of sensory neurons in limiting inflammation and promoting macrophage tissue-repair functions in the skin. She explained that the sensory nervous system also regulates the adaptive immune response to Herpes simplex virus type 1 infection. Her team is currently exploring the molecular and cellular basis of these neuro-immune regulations and the potential therapeutic value of their findings for the treatment of inflammatory diseases.
During the “High content imaging” session, Laura Kuett (University of Zurich, Switzerland) presented a new workflow of 3D imaging mass cytometry for cell-level mapping of tissues. She explained their experimental workflow based on thin sectioning of samples together with computational image analysis steps for image registration and segmentation to achieve single cell level 3D imaging mass cytometry models. By applying this workflow and underscoring advantage of this method on different breast cancer samples she revealed how it could be applied to studying tumor microenvironment and metastasis-associated events. These models capture the phenotypic complexity of breast tumors by enabling simultaneous mapping of tumor, immune and stromal cells in tissue volumes and reveal spatial interactions that can be elusive on 2D images.
Paulina Garcia Gonzalez (Centre d’Immunologie de Marseille-Luminy/ CNRS/ Aix-Marseille Université, Marseille) presented a new method they developed to assess metabolic state, epigenetics, and immune profiling at a single cell level of immune cells. Using a small amount of sample, they were able to determine the functional metabolic status of lymphocytes, B cells, DCs, monocytes, NK cells, neutrophils, and basophils in peripheral blood with high resolution. They also efficiently measured histone modification marks in parallel, without altering their puromycin reading, thus obtaining a single-cell readout of metabolism and epigenetic heterogeneity at the same time. Interestingly, each immune cell type analyzed displayed a distinctive pattern of histone modification as well as a particular metabolic profile.
Finally, I warmly thank the CFCD for their financial support that gave me the opportunity to participate in this congress. It was a great experience that allowed me to present my data during the poster sessions and discover many aspects of Immunology that I did not know.