Featured
-
-
Article
| Open AccessPulmonary inflammation promoted by type-2 dendritic cells is a feature of human and murine schistosomiasis
Schistosomiasis, a parasitic helminth infection, causes pulmonary symptoms during acute and chronic infection. Here, Houlder et al characterise the pulmonary immune response and demonstrate the role type 2 dendritic cells play in lung inflammation.
- E. L. Houlder
- , A. H. Costain
- & A. S. MacDonald
-
Article
| Open AccessMAIT cell inhibition promotes liver fibrosis regression via macrophage phenotype reprogramming
Liver cirrhosis is characterised by extensive fibrosis of the liver, and understanding the underpinning immunological processes is important in designing intervention. Here authors show that Mucosal-Associated Invariant T cells are instrumental to controlling the balance between profibrogenic and restorative macrophages and inhibiting their activation might reverse liver fibrosis.
- Morgane Mabire
- , Pushpa Hegde
- & Sophie Lotersztajn
-
Article
| Open AccessSingle-cell analysis of peripheral blood from high-altitude pulmonary hypertension patients identifies a distinct monocyte phenotype
Single cell transcriptomic sequencing (scRNA) can identify genes that are differentially expressed in cell populations in specific diseases. Here the authors perform scRNA sequencing in a high-altitude pulmonary hypertension (HAPH) cohort and show transcriptional differences in monocyte populations.
- Xin-Hua Wu
- , Yang-Yang He
- & Zhi-Cheng Jing
-
Article
| Open AccessPrimitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR
The generation of primitive macrophages remains a poorly understood process in humans. Here, the authors identify placental erythro-myeloid progenitors that give rise to foetal macrophages in the early human placenta and demonstrate that epigenetic silencing of the class II transactivator leads to downregulation of HLA-DR in these cells.
- Jake R. Thomas
- , Anna Appios
- & Naomi McGovern
-
Article
| Open AccessEarly life gut microbiota sustains liver-resident natural killer cells maturation via the butyrate-IL-18 axis
Liver-resident natural killer cells develop locally and have multiple immunological roles in situ. Here the authors investigate the gut-liver axis and show the impact of the intestinal microbiota on the development of liver-resident natural killer cells.
- Panpan Tian
- , Wenwen Yang
- & Xiaohong Liang
-
Article
| Open AccessTesticular macrophages are recruited during a narrow fetal time window and promote organ-specific developmental functions
How testis resident macrophages develop and influence tissue function is not fully understood. Here the authors use mouse lineage tracing methods to document the haematopoietic source, development and recruitment of early testicular macrophages, support of foetal testis differentiation, and interaction with, and promotion of steroidogenesis in, Leydig cells.
- Xiaowei Gu
- , Anna Heinrich
- & Tony DeFalco
-
Article
| Open AccessControl of human cytomegalovirus replication by liver resident natural killer cells
Natural killer cells play important roles in the immune response to human cytomegalovirus infection. Here the authors implicate donor-derived liver resident natural killer cells in the control of human cytomegalovirus infection by analysis of perfusates derived from human transplant livers.
- Calum Forrest
- , Thomas J. G. Chase
- & Matthew Reeves
-
Article
| Open AccessCTCF controls three-dimensional enhancer network underlying the inflammatory response of bone marrow-derived dendritic cells
The role of 3D genome organization is not well understood in the transcriptional regulation of dendritic cells. Here the authors show that activation of dendritic cells in vitro induces dynamic reprogramming of the chromatin looping and enhancer activity linked to changes in gene expression and implicates a role for the chromatin architecture protein CTCF in the inflammatory response of dendritic cells.
- Bobae Yang
- , Sueun Kim
- & Hyoung-Pyo Kim
-
Article
| Open AccessSerum/glucocorticoid-inducible kinase 1 deficiency induces NLRP3 inflammasome activation and autoinflammation of macrophages in a murine endolymphatic hydrops model
The immune response has been suggested to be involved in the pathology of Ménière’s disease. Here the authors implicate serum glucocorticoid-inducible kinase 1 as a regulator of the NLRP3 inflammasome and link to macrophage function in a model of Ménière’s disease pathology.
- Dao-Gong Zhang
- , Wen-Qian Yu
- & Hai-Bo Wang
-
Article
| Open AccessFluorinated polyamidoamine dendrimer-mediated miR-23b delivery for the treatment of experimental rheumatoid arthritis in rats
Delivery of anti-inflammatory microRNA (miRNA) could be beneficial for inflammatory diseases such as rheumatoid arthritis (RA). Here the authors show that a fluorinated polyamidoamine dendrimer nanoparticle delivers miR-23b to affected RA joints and reduces inflammation, joint damage and synovial cell influx.
- Haobo Han
- , Jiakai Xing
- & Quanshun Li
-
Article
| Open AccessGSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis
Macrophages have been shown to have an important function in atherosclerosis. Here the authors show that, in human atherosclerotic plaques and mouse models, GSDME and pyroptosis promote atherosclerosis and inhibition of these pathways could reduce pathology associated with atherosclerotic disease.
- Yuanyuan Wei
- , Beidi Lan
- & Yue Wu
-
Article
| Open AccessOxidized mitochondrial DNA induces gasdermin D oligomerization in systemic lupus erythematosus
Systemic lupus erythematosus is characterised by the generation of antibodies targeting DNA and nuclear antigens. Here, the authors show that oxidised mitochondrial DNA induces gasdermin D oligomerization and promotes pore formation in neutrophils from patients with SLE.
- Naijun Miao
- , Zhuning Wang
- & Jing Wang
-
Article
| Open AccessRemodeling articular immune homeostasis with an efferocytosis-informed nanoimitator mitigates rheumatoid arthritis in mice
Proinflammatory macrophages are involved in rheumatoid arthritis (RA). Here the authors use an efferocytosis-mimetic self-deliverable nanoimitator to mitigate RA by targeted reprogramming of synovial inflammatory macrophages, reducing proinflammatory cytokines and reinstating articular immune homeostasis.
- Shengchang Zhang
- , Ying Liu
- & Xinyi Jiang
-
Article
| Open AccessT cell-independent eradication of experimental glioma by intravenous TLR7/8-agonist-loaded nanoparticles
Glioblastoma is a highly aggressive, and also the most common, brain tumour type in adults. Here, the authors generate a nanoparticle encapsulating the TLR7/8 agonist, R848, which induces tumour regression in mice by reprogramming myeloid cells independently of T and NK cells.
- Verena Turco
- , Kira Pfleiderer
- & Michael Platten
-
Article
| Open AccessHIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC
HIV vaccine development can be aided by knowledge of correlates of protection. Here the authors identify engagement and reprogramming of tolerogenic CD14+ myeloid cells mediating a spatiotemporal balance of pro- and anti-inflammatory responses, as correlates of efficacy in female macaques vaccinated with the DNA/ALVAC/gp120/Alum platform.
- Massimiliano Bissa
- , Sohyoung Kim
- & Genoveffa Franchini
-
Article
| Open AccessInfluence of circadian clocks on adaptive immunity and vaccination responses
Circadian rhythms have been shown to influence immune responses, but it is unclear whether this influences responses to vaccines. Here the authors show that dendritic cells migrate in a circadian rhythm meaning that interactions with T cells are altered leading to differential vaccine responses.
- Louise Madeleine Ince
- , Coline Barnoud
- & Christoph Scheiermann
-
Article
| Open AccessIn vivo induction of activin A-producing alveolar macrophages supports the progression of lung cell carcinoma
Alveolar macrophages represent a cell type that is physiologic to the lung immune landscape, however, it is not known whether they play an active role to maintain the tumour immune microenvironment. Here authors show by single cell RNA sequencing and functional experiments, that intra-tumour alveolar macrophages are phenotypically and transcriptionally different from the healthy ones, and likely play an aetio-pathologic role in tumorigenesis.
- Seiji Taniguchi
- , Takahiro Matsui
- & Masaru Ishii
-
Article
| Open AccessCD4+ helper T cells endow cDC1 with cancer-impeding functions in the human tumor micro-environment
The presence of classical type 1 dendritic cells (cDC1) positively influences prognosis in cancer, but their intricate networking with the various T cell types found in the tumour microenvironment is not fully appreciated. Here the authors show that cDC1 encounter with CD4+ helper T-cells transforms their gene expression signature, and these “helped” dendritic cells enable the function of anti-tumour cytotoxic T-cells.
- Xin Lei
- , Indu Khatri
- & Yanling Xiao
-
Article
| Open AccessTranscriptional reprogramming from innate immune functions to a pro-thrombotic signature by monocytes in COVID-19
Although myeloid cell dysfunction has been observed in COVID-19, the underlying mechanisms remain incompletely understood. Here, the authors demonstrate that monocytes from patients with mild to moderate COVID-19 show a blunted innate immune response and a pro-thrombotic signature following secondary SARS-CoV-2 challenge.
- Allison K. Maher
- , Katie L. Burnham
- & Margarita Dominguez-Villar
-
Article
| Open AccessA genome-wide CRISPR screen identifies WDFY3 as a regulator of macrophage efferocytosis
Efferocytosis describes the engulfment and clearance of apoptotic cells by phagocytes. Here the authors identify in primary mouse macrophage WDFY3 as a regulator for efferocytosis, in which c-terminal WDFY3 is sufficient to modulate degradation while full-length WDFY3 is required to modulate the uptake of apoptotic cells.
- Jianting Shi
- , Xun Wu
- & Hanrui Zhang
-
Article
| Open AccessLocally organised and activated Fth1hi neutrophils aggravate inflammation of acute lung injury in an IL-10-dependent manner
Acute respiratory distress syndrome (ARDS) is an acute pulmonary disease involving neutrophils. Here the authors characterise lung neutrophil infiltration during ARDS and show that there are neutrophils with different function and transcriptional profile which are regulated by IL-10.
- Kun Wang
- , Muyun Wang
- & Wei Gao
-
Article
| Open AccessMyeloid cells promote interferon signaling-associated deterioration of the hematopoietic system
Innate and adaptive immune cells function in the homeostasis of haematopoietic stem cells (HSC). Here the authors show that myeloid cells are able to reduce the function of HSCs via interferon signaling through a neutrophil-NK cell dependent process.
- Jacqueline Feyen
- , Zhen Ping
- & Marc H. G. P. Raaijmakers
-
Article
| Open AccessMaturation and specialization of group 2 innate lymphoid cells through the lung-gut axis
The developmental process of group 2 innate lymphoid cells (ILC2) involves migration between different internal organs. Here the authors show that ILC2s migrate from the lung to the intestine to undergo maturation after treatment with IL-33 and that lung and intestine ILC2s have a different phenotype.
- Min Zhao
- , Fei Shao
- & Shuo Wang
-
Article
| Open AccessThe circadian clock influences T cell responses to vaccination by regulating dendritic cell antigen processing
Circadian rhythms are known to impact a range of biological processes including in the immune system. Here the authors show how circadian rhythms modulate the T cell response to vaccination via regulation of dendritic cell metabolism.
- Mariana P. Cervantes-Silva
- , Richard G. Carroll
- & Annie M. Curtis
-
Article
| Open AccessSingle-cell sequencing shows cellular heterogeneity of cutaneous lesions in lupus erythematosus
Discoid lupus erythematosus (DLE) and systemic LE (SLE) can present as cutaneous lesions. Here the authors characterise an scRNA dataset of cutaneous lesions from these patients and compare these to healthy controls showing differential immune cell recruitment, cell type and gene expression.
- Meiling Zheng
- , Zhi Hu
- & Ming Zhao
-
Article
| Open AccessNasal DNA methylation at three CpG sites predicts childhood allergic disease
Accurate prediction of the onset of childhood allergy is important to clarify the difference between various respiratory diseases. Here the authors propose that the methylation status of three sites in nasal DNA predicts the onset of childhood allergy which may aid diagnosis and monitoring.
- Merlijn van Breugel
- , Cancan Qi
- & Cheng-Jian Xu
-
Article
| Open AccessIntegrated proteomic and transcriptomic landscape of macrophages in mouse tissues
Macrophage is located in different tissue to serve diverse functions. Here the authors use mass spectrometry and bulk RNA-sequencing to profile 11 mouse macrophage populations from 8 tissues, and combine their de novo data with public datasets to report an integrated proteomic and transcriptomic landscape of mouse macrophage as a valuable resource.
- Jingbo Qie
- , Yang Liu
- & Chen Ding
-
Article
| Open AccessDeciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain
Perivascular macrophages (pvMs) are important for brain drainage and immune regulation. Here the authors analyse various reporter mouse strains for finer mapping of pvM subsets and lineage differentiation, and propose CX3CR1negative and CD45low as additional markers of intermediate pvMs for studying this heterogenous population.
- C. Siret
- , M. van Lessen
- & S. A. van de Pavert
-
Article
| Open AccessThe E3 ubiquitin ligase WWP2 regulates pro-fibrogenic monocyte infiltration and activity in heart fibrosis
Non-ischemic cardiomyopathy is a severe disease, characterized by interstitial fibrosis in the left ventricle of the heart. Here authors show that the E3 ubiquitin ligase WWP2 plays a pathogenic role in heart fibrosis via regulating a distinct monocyte population that initiates the process.
- Huimei Chen
- , Gabriel Chew
- & Enrico Petretto
-
Article
| Open AccessmTORC1 links pathology in experimental models of Still’s disease and macrophage activation syndrome
Still’s disease is an inflammatory syndrome linked to the development of further immune dysregulation and hypercytokinaemia termed macrophage activation syndrome. Here the authors implicate the mechanistic target of rapamycin complex 1 in murine models of Still’s disease and macrophage activation syndrome, and provide associations with clinical cases in patients
- Zhengping Huang
- , Xiaomeng You
- & Pui Y. Lee
-
Article
| Open AccessImmune phenotypes that are associated with subsequent COVID-19 severity inferred from post-recovery samples
The association of specific immune cell types with SARS-CoV-2 severity is not fully understood. Here the authors analyse PBMC from individuals recovered from COVID-19 and propose immune cell signatures post recovery that are associated with disease severity.
- Thomas Liechti
- , Yaser Iftikhar
- & Mario Roederer
-
Article
| Open AccessDefective activation and regulation of type I interferon immunity is associated with increasing COVID-19 severity
The interferon response has been shown to be linked to severity of SARS-CoV-2 infection and is an essential component of the immune response to COVID-19. Here the authors stratify patients according to COVID-19 severity and asses the interferon response showing defective responses in severe infection and highlight the importance of assay variables and confounding factors that impact the detection of interferon.
- Nikaïa Smith
- , Céline Possémé
- & Darragh Duffy
-
Article
| Open AccessAlveolar macrophage metabolic programming via a C-type lectin receptor protects against lipo-toxicity and cell death
Alveolar macrophages (AM) in the lungs maintain surfactant during homeostasis and respond to infectious pathogens. Here the authors show that in the absence of NKR-P1B, pneumococcal infection is more severe because KO AM have increased rates of lipid surfactant uptake and reduced anti-microbial function.
- Michal Scur
- , Ahmad Bakur Mahmoud
- & Andrew P. Makrigiannis
-
Article
| Open AccessDifferential compartmentalization of myeloid cell phenotypes and responses towards the CNS in Alzheimer’s disease
Multiple state-of-the-art analyses of immune cells in 117 blood, 117 cerebrospinal fluid, 13 choroid plexus and 13 brain parenchyma samples reveal differential characteristics of immune cells in different body compartments and different diseases.
- Camila Fernández Zapata
- , Ginevra Giacomello
- & Chotima Böttcher
-
Article
| Open AccessPolymeric micelles effectively reprogram the tumor microenvironment to potentiate nano-immunotherapy in mouse breast cancer models
Nanotherapy has potential utility in cancer, particularly in targeted delivery of therapeutics. Here the authors demonstrate delivery of tranilast loaded micelles to improve the reprogramming of cancer associated fibroblasts and monitor tumour stiffness to predict responses.
- Myrofora Panagi
- , Fotios Mpekris
- & Triantafyllos Stylianopoulos
-
Article
| Open AccessDepletion of CD206+ M2-like macrophages induces fibro-adipogenic progenitors activation and muscle regeneration
Muscle regeneration requires the contribution and communication of various different cell types. Here, Nawaz et al. show that CD206+ macrophages inhibit the secretion of the promyogenic factor follistatin by fibro-adipogenic progenitor cells, impeding myogenesis and muscle regeneration.
- Allah Nawaz
- , Muhammad Bilal
- & Kazuyuki Tobe
-
Article
| Open AccessNeutrophil breaching of the blood vessel pericyte layer during diapedesis requires mast cell-derived IL-17A
The blood vessel wall is a complex multi-layered structure, yet upon injury or infection, neutrophil leukocytes are rapidly migrating from the blood stream to the affected tissues, by a process termed diapedesis. Authors here show that the final steps of diapedesis through the outer pericyte layer is regulated by perivascular mast cells via IL-17A production.
- Régis Joulia
- , Idaira María Guerrero-Fonseca
- & Mathieu-Benoit Voisin
-
Article
| Open AccessPD-L1 negatively regulates antifungal immunity by inhibiting neutrophil release from bone marrow
Programmed death ligand 1 (PD-L1) suppresses host immunity during infection and microbial sepsis. Here, the authors show that PD-L1 does this by regulating the secretion of CXCL1 and CXCL2 to control neutrophil mobilization during Candida albicans infection.
- Yao Yu
- , Rong-Rong Wang
- & Xin-Ming Jia
-
Article
| Open AccessFerritin triggers neutrophil extracellular trap-mediated cytokine storm through Msr1 contributing to adult-onset Still’s disease pathogenesis
Hyperferritinemic syndrome is a collective term for a group of severe inflammatory conditions distinguished by high ferritin levels, including adult-onset Still’s disease and COVID-19. Here authors show in an animal model that high ferritin levels are not just a sign of hyperinflammation but also a pathogenic factor that triggers neutrophil leukocyte activation and extracellular trap formation.
- Jinchao Jia
- , Mengyan Wang
- & Qiongyi Hu
-
Article
| Open AccessCDKN1A is a target for phagocytosis-mediated cellular immunotherapy in acute leukemia
Inducing phagocytic capacities of tumour-associated macrophages to eliminate cancer cells is a promising immunotherapy. Here, the authors show that engineered macrophages overexpressing CDKN1A/p21 reduce leukaemic tumour burden and increase survival in preclinical mouse models of human T-ALL.
- Awatef Allouch
- , Laurent Voisin
- & Jean-Luc Perfettini
-
Article
| Open AccessCD1d-dependent rewiring of lipid metabolism in macrophages regulates innate immune responses
Modulation of metabolic pathways is linked to regulation of immune cells including macrophages. Here the authors identify a role for CD1d in the metabolic rewiring of macrophages, which alters responsiveness to innate stimuli.
- Phillip M. Brailey
- , Lauren Evans
- & Patricia Barral
-
Article
| Open AccessTumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer
Dendritic cells (DC) present tumour antigens to T cells but this process is defective in the tumour microenvironment. Here the authors find that downregulation of cholesterol 25-hydroxylase underlies defective cross presentation of tumour antigens.
- Zhen Lu
- , Jinyun Chen
- & Serge Y. Fuchs
-
Article
| Open AccessA genetically encoded fluorescent biosensor for detecting itaconate with subcellular resolution in living macrophages
Itaconate has been identified as an immunomodulatory metabolite produced by activated macrophages, but methods for detecting itaconate in live cells are lacking. Here, the authors develop a fluorescent biosensor named BioITA for detecting itaconate in subcellular compartments of living macrophages.
- Pengkai Sun
- , Zhenxing Zhang
- & Xinjian Li
-
Article
| Open Accessvon Willebrand factor links primary hemostasis to innate immunity
von Willebrand factor (VWF) plays a critical role in primary hemostasis following vascular injury by tethering platelets to exposed collagen. Here, VWF binding to macrophages is shown to trigger NF-κB activation and induce pro-inflammatory responses.
- Clive Drakeford
- , Sonia Aguila
- & James S. O’Donnell
-
Article
| Open AccessJAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm
JAK2V617F mutation is associated with an increased risk for athero-thrombotic cardiovascular disease, but its role in aortic disease development remains unknown. Here, the authors show that JAK2V617F mutation drives vascular resident macrophages toward a pathogenic phenotype and promotes dissecting aortic aneurysm.
- Rida Al-Rifai
- , Marie Vandestienne
- & Hafid Ait-Oufella
-
Article
| Open AccessUnderstanding fibrosis pathogenesis via modeling macrophage-fibroblast interplay in immune-metabolic context
Renal fibrosis is a progressive process with complex etiopathology, causing organ failure. Here authors present a mathematical model, based on an in vitro system faithfully contemplating macrophage-fibroblast interaction and the metabolic-immunologic signals that are affecting kidney fibrosis, that is applicable to kidney transplant failure.
- Elisa Setten
- , Alessandra Castagna
- & Massimo Locati
-
Article
| Open AccessNeuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma
Responses to immune checkpoint blockade (ICB) in patients with glioblastoma are limited. Here the authors show that Calmodulin-Dependent Kinase Kinase 2 (CaMKK2) is expressed in tumor associated macrophages and neurons and is associated with resistance to ICB in preclinical models of glioblastoma.
- William H. Tomaszewski
- , Jessica Waibl-Polania
- & John H. Sampson
-
Article
| Open AccessGPR97 triggers inflammatory processes in human neutrophils via a macromolecular complex upstream of PAR2 activation
Activation of neutrophil leukocytes is tightly regulated, and it is important to understand the molecular mechanisms of their response to physiological and pathological stimuli. Here authors show that the adhesion molecule G protein-coupled receptor 97 and its interaction partners play pivotal roles in neutrophil leukocyte activation both in anti-microbial response and in inflammatory diseases.
- Tai-Ying Chu
- , Céline Zheng-Gérard
- & Hsi-Hsien Lin
-
Article
| Open AccessMetabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion
Chemo-resistance and immune evasion are major challenges in osteosarcoma treatment. Here the authors show that doxorubicin promotes IL-18 secretion by tumor associated macrophages inducing LAT2-dependent CD47 upregulation in osteosarcoma cells, suggesting LAT2 inhibition as a therapeutic option in combination with doxorubicin.
- Zenan Wang
- , Binghao Li
- & Zhaoming Ye