Immunology

Written by Claire Kowalick A breakthrough for biomedical research promises new insight into immunotherapy development and disease modeling. Scientists at The University of Texas Health Science Center at San Antonio have created a humanized mouse model with a human immune system and a human-like gut microbiome that is capable of mounting specific antibody responses. The scientists […]

Natural killer (NK) cells are innate lymphoid cells (ILCs) that serve as a first line of defense against pathogens and tumors. Historically, their classification hinged on a limited array of surface protein markers. However, recent advancements in single-cell technologies, such assingle-cell RNA sequencing (scRNA-seq) and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), have unveiled a more complex and nuanced understanding of NK cells. This has led to variations in nomenclature and inconsistencies across scientific literature. In our study, we utilized these technologies to dissect the heterogeneity of NK cells in healthy human blood. We identified three prominent NK cell subsets: NK1, NK2 and NK3, further differentiated into six distinct subgroups. All subsets were present in all donors, irrespective of their human cytomegalovirus (HCMV) status. Our findings delineate the unique molecular characteristics, key transcription factors, principal biological functions, significant metabolic traits, and cytokine responses of each subgroup. These data also suggest two separate ontogenetic origins for NK cells, leading to divergent transcriptional trajectories. We explore these pathways in depth and propose a comprehensive, standardized nomenclature for NK cells. This standardized terminology aims at fostering clarity and consistency in future research, thereby improving cross-study comparisons.

Influenza virus infection is initiated by the attachment of the viral haemagglutinin (HA) protein to sialic acid receptors on the host cell surface. Most virus particles enter cells through clathrin-mediated endocytosis (CME). However, it is unclear how viral binding signals are transmitted through the plasma membrane triggering CME. Here we found that metabotropic glutamate receptor subtype 2 (mGluR2) and potassium calcium-activated channel subfamily M alpha 1 (KCa1.1) are involved in the initiation and completion of CME of influenza virus using an siRNA screen approach. Influenza virus HA directly interacted with mGluR2 and used it as an endocytic receptor to initiate CME. mGluR2 interacted and activated KCa1.1, leading to polymerization of F-actin, maturation of clathrin-coated pits and completion of the CME of influenza virus. Importantly, mGluR2-knockout mice were significantly more resistant to different influenza subtypes than the wild type. Therefore, blocking HA and mGluR2 interaction could be a promising host-directed antiviral strategy. Influenza virus uses metabotropic glutamate receptor 2 (mGluR2) as an endocytic receptor to enter cells through clathrin-mediated endocytosis.

Summary. Basophils are the rarest leukocytes, but they have essential roles in protection against helminths, allergic disorders, autoimmune diseases, and s

CD4 T helper cells use the SNARE protein SYNTAXIN-11 to promote B cell differentiation, germinal center formation, and class switching by facilitating CD40

A Blueprint for #Tumor-Infiltrating #Bcells across Human #Cancers | Breaking OPEN ACCESS Study Online Now at Science Magazine + Accompanying OPEN ACCESS…

Today we celebrate the incredible advancements in immunology that help protect us from disease and pave the way for healthier futures.

Day of Immunology Celebrate your amazing immune system on the 29 April by attending events around Australia and New Zealand. Established in 2005 by the European Federation of Immunological Societies (EFIS), the success of Day of Immunology led to it being celebrated worldwide since 2007.

Eosinophils are bone marrow-derived granulocytes that are traditionally associated with type 2 immune responses, such as those that occur during parasite infections and allergy. Emerging evidence demonstrates the remarkable functional plasticity of this elusive cell type and its pleiotropic functions in diverse settings. Eosinophils broadly contribute to tissue homeostasis, host defence and immune regulation, predominantly at mucosal sites. The scope of their activities primarily reflects the breadth of their portfolio of secreted mediators, which range from cytotoxic cationic proteins and reactive oxygen species to multiple cytokines, chemokines and lipid mediators. Here, we comprehensively review basic eosinophil biology that is directly related to their activities in homeostasis, protective immunity, regeneration and cancer. We examine how dysregulation of these functions contributes to the physiopathology of a broad range of inflammatory diseases. Furthermore, we discuss recent findings regarding the tissue compartmentalization and adaptation of eosinophils, shedding light on the factors that likely drive their functional diversification within tissues. This Review by Arnold and Munitz discusses the diverse roles of eosinophils in the settings of tissue homeostasis, infection, allergy and cancer. The authors explain the molecular mechanisms that enable eosinophils to adapt to diverse tissue types and conditions, and they consider the therapeutic potential of eosinophil-depleting drugs in the clinic.

Tumours can obtain nutrients and oxygen required to progress and metastasize through the blood supply1. Inducing angiogenesis involves the sprouting of established vessel beds and their maturation into an organized network2,3. Here we generate a comprehensive atlas of tumour vasculature at single-cell resolution, encompassing approximately 200,000 cells from 372 donors representing 31 cancer types. Trajectory inference suggested that tumour angiogenesis was initiated from venous endothelial cells and extended towards arterial endothelial cells. As neovascularization elongates (through angiogenic stages SI, SII and SIII), APLN+ tip cells at the SI stage (APLN+ TipSI) advanced to TipSIII cells with increased Notch signalling. Meanwhile, stalk cells, following tip cells, transitioned from high chemokine expression to elevated TEK (also known as Tie2) expression. Moreover, APLN+ TipSI cells not only were associated with disease progression and poor prognosis but also hold promise for predicting response to anti-VEGF therapy. Lymphatic endothelial cells demonstrated two distinct differentiation lineages: one responsible for lymphangiogenesis and the other involved in antigen presentation. In pericytes, endoplasmic reticulum stress was associated with the proangiogenic BASP1+ matrix-producing pericytes. Furthermore, intercellular communication analysis showed that neovascular endothelial cells could shape an immunosuppressive microenvironment conducive to angiogenesis. This study depicts the complexity of tumour vasculature and has potential clinical significance for anti-angiogenic therapy. An atlas of tumour vasculature shows that tumour angiogenesis is initiated from venous endothelial cells and extended towards arterial endothelial cells.

Proinflammatory cytokines and chemokines play a crucial role in regulating the inflammatory response, which is essential for the proper functioning of our immune system. When infections or threats to the body’s defense mechanisms are detected, the innate immune system takes the lead. However, an excessive inflammatory response can lead to the production of high concentrations of cytotoxic molecules, resulting in tissue damage. Inflammasomes are significant contributors to innate immunity, and one of the most extensively studied inflammasome complexes is NOD-like receptor 3 (NLRP3). NLRP3 has a wide range of recognition mechanisms that streamline immune activation and eliminate pathogens. These cytosolic multiprotein complexes are composed of effector, adaptor, and sensor proteins, which are crucial for identifying intracellular bacterial breakdown products and initiating an innate immune cascade. To understand the diverse behavior of NLRP3 activation and its significance in the development of lifestyle-related diseases, one must delve into the study of the immune response and apoptosis mediated by the release of proinflammatory cytokines. In this review, we briefly explore the immune response in the context of lifestyle associated disorders such as obesity, hyperlipidemia, diabetes, chronic respiratory disease, oral disease, and cardiovascular disease. NOD-like receptors (NLRs - proteins that help our immune system fight off harmful invaders) are vital for our health. Their function in T and B cells (types of white blood cells) is less clear. Scientists have found 22 kinds of NLRs in humans, which start different immune and inflammation responses. This study is a detailed review of NLRs, examining their structure, how they are activated, and their role in diseases like obesity, diabetes, and heart problems. It emphasizes that NLRs, particularly the NLRP3 inflammasome (a protein complex involved in inflammation), are key in lifestyle diseases by causing inflammation. The review proposes that focusing on NLRP3 could lead to new treatments for these diseases. This research is a big step in understanding how our natural immune system contributes to chronic diseases and offers potential for new treatments. Future research could further explore the complexities of NLRs and their potential as treatment targets. This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.

Phagocytosis is the process by which myeloid phagocytes bind to and internalize potentially dangerous microorganisms1. During phagocytosis, innate immune receptors and associated signalling proteins are localized to the maturing phagosome compartment, forming an immune information processing hub brimming with microorganism-sensing features2–8. Here we developed proximity labelling of phagosomal contents (PhagoPL) to identify proteins localizing to phagosomes containing model yeast and bacteria. By comparing the protein composition of phagosomes containing evolutionarily and biochemically distinct microorganisms, we unexpectedly identified programmed death-ligand 1 (PD-L1) as a protein that specifically enriches in phagosomes containing yeast. We found that PD-L1 directly binds to yeast upon processing in phagosomes. By surface display library screening, we identified the ribosomal protein Rpl20b as a fungal protein ligand for PD-L1. Using an auxin-inducible depletion system, we found that detection of Rpl20b by macrophages cross-regulates production of distinct cytokines including interleukin-10 (IL-10) induced by the activation of other innate immune receptors. Thus, this study establishes PhagoPL as a useful approach to quantifying the collection of proteins enriched in phagosomes during host–microorganism interactions, exemplified by identifying PD-L1 as a receptor that binds to fungi. Proximity labelling of phagosomal contents is used to identify proteins that localize to phagosomes in host–microorganism interactions.

The majority of cancer patients receive radiotherapy. Wang et al. review preclinical and clinical data related to the importance of immune responses to rad

Leukocyte migration is a fundamental component of innate and adaptive immune responses as it governs the recruitment and localization of these motile cells, which is crucial for immune cell priming, effector functions, memory responses and immune regulation. This complex cellular trafficking system is controlled to a large extent via highly regulated production of secreted chemokines and the restricted expression of their membrane-tethered G-protein-coupled receptors. The activity of chemokines and their receptors is also regulated by a subfamily of molecules known as atypical chemokine receptors (ACKRs), which are chemokine receptor-like molecules that do not couple to the classical signalling pathways that promote cell migration in response to chemokine ligation. There has been a great deal of progress in understanding the biology of these receptors and their functions in the immune system in the past decade. Here, we describe the contribution of the various ACKRs to innate and adaptive immune responses, focussing specifically on recent progress. This includes recent findings that have defined the role for ACKRs in sculpting extracellular chemokine gradients, findings that broaden the spectrum of chemokine ligands recognized by these receptors, candidate new additions to ACKR family, and our increasing understanding of the role of these receptors in shaping the migration of innate and adaptive immune cells. This Review from Comerford and McColl discusses recent advances that have been made in understanding the biology of the atypical chemokine receptor (ACKR) family. The authors explain how these receptors interact with their ligands to shape immune responses and also highlight potential new additions to the ACKR family.

This work reveals that human effector CD8 T cells not only mediate cytotoxicity but also promote tissue remodeling. The remodeling potential was demonstrat

29 avril 2024 | 2h00 - 4h30 CET | En ligne