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| 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
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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
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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
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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
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| 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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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| 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
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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
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| 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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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Article
| Open AccessBlood monocyte-derived CD169+ macrophages contribute to antitumor immunity against glioblastoma
Tumor-associated macrophages are believed to promote tumour progression and to hamper immune therapy in gliomas. Here authors identify a distinct population of macrophages within the glioblastoma immune microenvironment with antitumour properties and clearly distinguishable phenotypes and gene expression patterns from tumour promoting macrophages.
- Hyun-Jin Kim
- , Jang Hyun Park
- & Heung Kyu Lee
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Article
| Open AccessCancer co-opts differentiation of B-cell precursors into macrophage-like cells
The tumour microenvironment has been shown to change the phenotypes and functionality of immune cells to enable tumour propagation. Here authors show that cancers can derail B cell development to give rise to macrophage-like cells, contributing to cancer progression and metastasis via disabling local T cell response.
- Chen Chen
- , Bongsoo Park
- & Arya Biragyn
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Article
| Open AccessAdipocyte-derived lactate is a signalling metabolite that potentiates adipose macrophage inflammation via targeting PHD2
Adipocyte tissue macrophages (ATM) are recruited and activated in obesity. The authors show that adipocytes release lactate as a signal of inflammation and that this metabolite can enhance obesity associated inflammation through stimulation of ATM by direct binding with PHD2.
- Tianshi Feng
- , Xuemei Zhao
- & Xiaoyan Hui
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Article
| Open AccessTranscription-independent regulation of STING activation and innate immune responses by IRF8 in monocytes
The transcription factor IRF8 has been shown to regulate monocyte differentiation via its DNA-binding activity. Here authors show that IRF8 is also involved in cytosolic DNA sensing via its phosphorylation-dependent association to the adaptor protein STING, thus representing an important checkpoint between immune response and autoimmunity in monocytes.
- Wei-Wei Luo
- , Zhen Tong
- & Yan-Yi Wang
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Article
| Open AccessA single-cell atlas of the multicellular ecosystem of primary and metastatic hepatocellular carcinoma
The immune cell constituents and localisation within human hepatocellular carcinoma is not fully understood. Here the authors use single cell RNA sequencing of HCC from four different tissue sites and show differences between primary and metastatic tumours, tumour associated macrophages and immune cell populations.
- Yiming Lu
- , Aiqing Yang
- & Gangqiao Zhou
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Article
| Open AccessSpatiotemporal dynamics of macrophage heterogeneity and a potential function of Trem2hi macrophages in infarcted hearts
Cellular composition and function are not clearly defined in heart failure after myocardial infarction. Here, using single cell and spatial transcriptomics in a MI-HF mouse model, the authors show that macrophages expressing Trem2 are found within the infarcts and this could be a useful biomarker.
- Seung-Hyun Jung
- , Byung-Hee Hwang
- & Yeun-Jun Chung
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Article
| Open AccessPregnancy-induced maternal microchimerism shapes neurodevelopment and behavior in mice
During pregnancy, maternal cells are transferred to the fetus, where they can reach the developing brain. In this study, the authors demonstrate that these maternal cells play an important role in neurodevelopment.
- Steven Schepanski
- , Mattia Chini
- & Petra C. Arck
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Article
| Open AccessCancer immune therapy using engineered ‛tail-flipping’ nanoliposomes targeting alternatively activated macrophages
Tumor-associated macrophages are mostly pro-tumorigenic, due to their re-programming by the tumor microenvironment. Here authors show that nanoliposomes, incorporating phospholipids with a flipping-tail chain, are engulfed specifically by intratumoral, alternatively activated macrophages, while delivering a cargo that converts these cells into anti-tumor macrophages.
- Praneeth R. Kuninty
- , Karin Binnemars-Postma
- & Jai Prakash
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Article
| Open AccessIn mouse chronic pancreatitis CD25+FOXP3+ regulatory T cells control pancreatic fibrosis by suppression of the type 2 immune response
The function of T regulatory cells in the tissue fibrosis in chronic pancreatitis is not fully understood. Here the authors use a mouse model of chronic pancreatitis to show that Treg cells reduce IL-4 mediated chronic inflammation in the pancreas associated with M2-like macrophages in vivo.
- Juliane Glaubitz
- , Anika Wilden
- & Matthias Sendler
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Article
| Open AccessPathogen-selective killing by guanylate-binding proteins as a molecular mechanism leading to inflammasome signaling
Guanylate-binding proteins (GBP) have a function in inflammasome formation and pathogen defence. Here the authors show that these GBP proteins are able to kill certain bacteria and promote selective inflammasome activation and that this is mediated by specific GBP protein regions.
- Shouya Feng
- , Daniel Enosi Tuipulotu
- & Si Ming Man
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Article
| Open AccessGata6+ resident peritoneal macrophages promote the growth of liver metastasis
GLPMs represent a population of fetal liver derived large peritoneal cavity Gata6+ macrophages, with the capacity to invade the tissues they surround. Here, in experimental colon cancer liver metastasis models, the authors show that GLPMs invade liver metastasis directly from the peritoneum, promoting liver metastases growth.
- Mokarram Hossain
- , Raymond Shim
- & Paul Kubes
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Article
| Open AccessPostmitotic differentiation of human monocytes requires cohesin-structured chromatin
How chromatin structure and gene accessibility changes during monocyte differentiation is not clearly defined. Here the authors characterize the chromatin changes during macrophage or dendritic cell maturation from monocytes and the dependence of this upon cohesin and CTCF.
- Julia Minderjahn
- , Alexander Fischer
- & Michael Rehli
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Article
| Open AccessCalcium/calmodulin-dependent protein kinase IV promotes imiquimod-induced psoriatic inflammation via macrophages and keratinocytes in mice
Calcium/calmodulin-dependent protein kinase IV (CaMK4) has been shown to be involved in autoimmunity but it is not clear how it functions in psoriasis. Here the authors show that CaMK4 is increased in psoriasis and promotes inflammatory responses in mouse models of psoriasis mediated through macrophages and keratinocytes.
- Liang Yong
- , Yafen Yu
- & Liangdan Sun
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Article
| Open AccessMouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9
The role of IL-9 in the tumor microenvironment and its effects on macrophages remains unclear. Here, the authors show that IL-9 promotes the expansion of pulmonary macrophages and that targeting the IL-9R/arginase 1 axis restricts tumor growth, thus identifying this cytokine pathway as a potential therapeutic target.
- Yongyao Fu
- , Abigail Pajulas
- & Mark H. Kaplan
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Article
| Open AccessKir2.1-mediated membrane potential promotes nutrient acquisition and inflammation through regulation of nutrient transporters
Potassium channels and membrane potential may influence macrophage function during inflammation. Here the authors show that the Kir2.1 potassium channel affects macrophage metabolism by altering cell surface retention of nutrient transporters and subsequently regulates inflammatory disease responses.
- Weiwei Yu
- , Zhen Wang
- & Di Wang
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Article
| Open AccessEfferocytosis requires periphagosomal Ca2+-signaling and TRPM7-mediated electrical activity
Efficient removal of apoptotic cells by phagocytosis underlies tissue development, wound repair, host defense and organ homeostasis. Here, authors identify TRPM7 as a regulator of cargo acidification and Ca2+ signaling during apoptotic cell clearance.
- Michael S. Schappe
- , Marta E. Stremska
- & Bimal N. Desai
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Article
| Open AccessTargeting parvalbumin promotes M2 macrophage polarization and energy expenditure in mice
Exercise increases energy expenditure and suppresses obesity, but the effector mechanisms are not still unclear. Here the authors profile serum proteomics in exercised mice to find reduced parvalbumin levels that correlate with increased M2 macrophage and suppressed diet-induced obesity to hint parvalbumin as a potential therapy target against obesity.
- Shaojian Lin
- , Anke Zhang
- & Bing Luan
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Article
| Open AccessMacrophages disseminate pathogen associated molecular patterns through the direct extracellular release of the soluble content of their phagolysosomes
The detection of conserved motifs by pattern recognition receptors is a crucial component of the innate detection of pathogens and danger signals via conserved pattern recognition receptors. Here the authors define a pathway that transfers partially digested material from the phagolysosomal pathway of macrophages to release at the plasma membrane which is associated with enhanced inflammatory potential, by a process they introduce as eructophagy.
- Catherine J. Greene
- , Jenny A. Nguyen
- & Robin M. Yates
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Article
| Open AccessDifferential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model
Model systems to study SARS-CoV-2 infection are required to better understand the immune response. Here the authors use a lung and macrophage co-culture system by differentiation of human pluripotent stem cells to better understand the phenotype and gene expression changes in host lung cells and macrophages after SARS-CoV-2 infection in vitro.
- Qizhou Lian
- , Kui Zhang
- & Huanhuan Joyce Chen
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Article
| Open AccessLung type II alveolar epithelial cells collaborate with CCR2+ inflammatory monocytes in host defense against poxvirus infection
Smallpox is a highly contagious respiratory pathogen associated with a high mortality rate. Here the authors utilize a mouse model of intranasal vaccinia virus infection and show a C7 gene encoded virulence factor attenuates type I IFN release by lung type II alveolar epithelial cells and reduces lung inflammatory monocyte responses.
- Ning Yang
- , Joseph M. Luna
- & Liang Deng
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Article
| Open AccessThe arginine methyltransferase PRMT7 promotes extravasation of monocytes resulting in tissue injury in COPD
Chronic obstructive pulmonary disease is a progressive and incurable chronic condition that involves accumulation of inflammatory macrophages in the lung tissue. Authors here show in mouse models of lung disease that PRMT7, a protein arginine methyltransferase, is an important regulator of recruitment and the pro-inflammatory phenotype of macrophages.
- Gizem Günes Günsel
- , Thomas M. Conlon
- & Ali Önder Yildirim