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| Open AccessCX3CR1 deficiency promotes muscle repair and regeneration by enhancing macrophage ApoE production
Chemokine-driven infiltration of inflammatory macrophages is central to the muscle regenerative response to injury. Here the authors show that the function of infiltrating macrophages is also important as notexin-induced muscle injury in mice is rescued by CX3CR1 knockout owing to enhanced ApoE production.
- Ludovic Arnold
- , Hélène Perrin
- & Christophe Combadiere
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| Open AccessTRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation
Transcriptional regulation of the interferon-β gene (Ifnb1) in macrophages is a critical immune event. Here, Ferri et al. show that, at late phases of macrophages activation, TRIM33 bound to a distal repressor element suppresses Ifnb1transcription by preventing recruitment of CBP/p300.
- Federica Ferri
- , Aude Parcelier
- & Paul-Henri Romeo
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| Open AccessHuman caspase-4 and caspase-5 regulate the one-step non-canonical inflammasome activation in monocytes
Human monocytes exhibit an unconventional one-step pathway of inflammasome activation and IL-1 release in response to LPS. Here the authors show that it is mediated by caspases 4 and 5, and characterize caspase 5 cleavage, Syk and calcium signalling as key mediators of this pathway.
- Elena Viganò
- , Catherine Emma Diamond
- & Alessandra Mortellaro
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| Open AccessmiR-142-5p and miR-130a-3p are regulated by IL-4 and IL-13 and control profibrogenic macrophage program
Fibroblast activity is regulated by tissue macrophages. Here the authors show that two miRNAs regulated by IL-4 and IL-13 in macrophages target SOCS1 and PPARγ and modulate profibrogenic macrophage program in vitro and in vivo, and that alterations of these miRNAs are found in fibrosis.
- Shicheng Su
- , Qiyi Zhao
- & Erwei Song
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| Open AccessIntestinal macrophages arising from CCR2+ monocytes control pathogen infection by activating innate lymphoid cells
Monocytes are important for antimicrobial host defence in the intestine but the mechanism behind their protective function is not fully understood. Seo et al. show that intestinal macrophages derived from CCR2+ monocytes support clearance of pathogenic Citrobacter rodentiumthrough activation of group 3 innate lymphoid cells.
- Sang-Uk Seo
- , Peter Kuffa
- & Nobuhiko Kamada
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| Open AccessIL10-driven STAT3 signalling in senescent macrophages promotes pathological eye angiogenesis
Pathological neovascularization causes blinding eye disease. Here the authors show that IL10 activates STAT3 signalling in the macrophages in the ageing eye, promoting their polarization towards a pro-angiogenic phenotype; interfering with this pathway reverses the pathology in a mouse model.
- Rei Nakamura
- , Abdoulaye Sene
- & Rajendra S. Apte
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| Open AccessIntestinal CD169+ macrophages initiate mucosal inflammation by secreting CCL8 that recruits inflammatory monocytes
Macrophages and dendritic cells residing in the lamina propria are involved in controlling mucosal immune balance. Here, the authors identify CD169+macrophages as contributors to the inflammation of DSS colitis through their role in mediating the recruitment of monocytes by secreting the cytokine CCL8.
- Kenichi Asano
- , Naomichi Takahashi
- & Masato Tanaka
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| Open AccessFunctional genomics identifies negative regulatory nodes controlling phagocyte oxidative burst
Phagocytes employ multiple bactericidal mechanisms to kill microorganisms, including the generation of toxic superoxide and other reactive oxygen species. Here the authors utilize a multi-omics approach to identify and characterize new regulatory nodes implicated in mucosal immunity that control phagocyte oxidative burst.
- Daniel B. Graham
- , Christine E. Becker
- & Ramnik J. Xavier
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The matricellular protein CCN1 mediates neutrophil efferocytosis in cutaneous wound healing
Neutrophils are the first line of response to injury but their persistence can inhibit the resolution phase of tissue repair. Here the authors show that an extracellular matrix protein promotes neutrophil clearance by macrophages, serving as a bridge between the two cell types and speeding up tissue repair.
- Joon-Il Jun
- , Ki-Hyun Kim
- & Lester F. Lau
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Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages
Activation of innate immune responses is subject to versatile regulation. Here the authors show that a conserved LATS family kinase Stk38 limits proinflammatory signalling downstream of TLR9 in macrophages and protects mice from lethal sepsis by MEKK2 ubiquitination and degradation.
- Mingyue Wen
- , Xianwei Ma
- & Huazhang An
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Alternatively activated macrophages promote pancreatic fibrosis in chronic pancreatitis
Chronic pancreatitis is an inflammatory disease accompanied by fibrosis. Here the authors show that pancreatic stellate cells produce IL-4 and IL-13 that trigger alternative activation of macrophages, and that genetic or pharmacological inhibition of IL-4/IL-13 signaling ameliorates the disease.
- Jing Xue
- , Vishal Sharma
- & Aida Habtezion
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Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation
The inflammasomes are multiprotein structures that trigger inflammation in response to diverse stress conditions. Here, Ip and Medzhitov show that the NLRP3 and NLRC4 inflammasomes in macrophages act as sensors of hyperosmotic stress and participate in salt-induced inflammatory responses.
- W. K. Eddie Ip
- & Ruslan Medzhitov
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ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms
The life cycle of parasitic hookworms includes a developmental stage in the lungs, before reaching the gut where they mature into adults. Here Bouchery et al. show that Group 2 innate lymphoid cells (ILC2s) cooperate with CD4+T cells to inhibit the development of a model hookworm in the lungs of mice.
- Tiffany Bouchery
- , Ryan Kyle
- & Graham Le Gros
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Article
| Open AccessAPOBEC3A cytidine deaminase induces RNA editing in monocytes and macrophages
Aberrant RNA editing is linked to a range of neuropsychiatric and chronic diseases. Here Sharma et al. show that APOBEC3A can function as an RNA editing protein in response to physiological stimuli, significantly expanding our understanding of RNA editing and the role this may play in diseases.
- Shraddha Sharma
- , Santosh K. Patnaik
- & Bora E. Baysal
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| Open AccessLRH-1 mediates anti-inflammatory and antifungal phenotype of IL-13-activated macrophages through the PPARγ ligand synthesis
Macrophages activate gene expression of alternative activation program in response to IL-13. Here the authors show that Liver Receptor Homologue-1 regulates synthesis of lipid metabolites stimulating antifungal and repressing proinflammatory genes in macrophages exposed to IL-13 through PPAR activation.
- Lise Lefèvre
- , Hélène Authier
- & Agnès Coste
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| Open AccessMyeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization
In response to microbial ligands, IRF5 promotes pro-inflammatory M1 macrophage activation and production of nitrous oxide. Here the authors show that nitrous oxide modifies IRF5 tyrosine residues as a negative feedback, limiting the inflammatory response and protecting from endotoxin shock.
- Geming Lu
- , Ruihua Zhang
- & Huabao Xiong
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Article
| Open AccessMolecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature
Neutrophil extracellular traps (NETs) released by neutrophils trap pathogens but may also cause tissue damage. Here the authors show that during systemic Staphylococcus aureusinfection NETs anchoring to the vasculature are only partially DNase-sensitive, advocating for better anti-NET therapies.
- Elzbieta Kolaczkowska
- , Craig N. Jenne
- & Paul Kubes
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| Open AccessXanthine oxidoreductase regulates macrophage IL1β secretion upon NLRP3 inflammasome activation
Activation of NLRP3 inflammasome requires generation of reactive oxygen species. Here the authors show that microbial or tissue damage-derived signals activate xanthine oxidase, which serves as a critical source of reactive oxygen species for inflammasome activation in macrophages.
- Annette Ives
- , Johji Nomura
- & Alexander So
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IRF8 directs stress-induced autophagy in macrophages and promotes clearance of Listeria monocytogenes
Autophagy is critical for pathogen clearance by innate immune cells. Here the authors show that IRF8 is activated in response to autophagy-inducing stimuli, promotes autophagic progression by driving transcription of autophagy genes and is critical for clearance of intracellular bacteria.
- Monica Gupta
- , Dong-Mi Shin
- & Keiko Ozato
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| Open AccessIL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology
Macrophages and dendritic cells contribute to gut homeostasis and mucosal immune defense. Here, Aychek et al. describe an IL-23-based crosstalk between these cells that prevents lethal immunopathology during Citrobacter rodentiuminfection.
- Tegest Aychek
- , Alexander Mildner
- & Steffen Jung
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Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages
Macrophages have a role in the pathogenesis of pulmonary emphysema. Here the authors show that inhalation—but not oral delivery—of the anti-osteoporosis drug alendronate attenuates lung damage in a mouse model of emphysema by inducing apoptosis of alveolar macrophages.
- Manabu Ueno
- , Toshitaka Maeno
- & Masahiko Kurabayashi
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The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity
ABCG1 transporter pumps cholesterol out of the cell. Here, the authors show that ABCG1-deficient mice have reduced tumour growth due to a switch of the tumour-associated macrophages from a tumour-promoting to tumour-suppressing phenotype, and are protected from the pro-tumorigenic effects of a Western-like diet.
- Duygu Sag
- , Caglar Cekic
- & Catherine C. Hedrick
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Article
| Open AccessUltrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets
Antigenic peptides are loaded into major histocompatibility complex class I (MHC I) molecules after entering the ER via the TAP transporter. Here, Fischbach et al. develop a flow cytometry assay to monitor TAP-dependent peptide translocation that is sensitive enough to use on scarce primary cell subsets.
- Hanna Fischbach
- , Marius Döring
- & Robert Tampé
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Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages
Activation of purinergic P2X7 receptors is important for phagocytosis and bacterial killing. Here the authors show that a phospholipid scramblase, Anoctamin 6, is activated downstream of P2X7R and is a critical mediator of bacterial internalization and killing by macrophages.
- Jiraporn Ousingsawat
- , Podchanart Wanitchakool
- & Karl Kunzelmann
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HIV-1 Tat inhibits phagocytosis by preventing the recruitment of Cdc42 to the phagocytic cup
Phagocytic activity of macrophages is reduced in HIV-1-infected patients, but the reason for this is unknown. Here, the authors report that secreted Tat protein inhibits phagocytosis by binding to the phospholipid PI(4,5)P2and impairing the recruitment of small GTPase Cdc42 to the phagocytic cup.
- Solène Debaisieux
- , Simon Lachambre
- & Bruno Beaumelle
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Proinflammatory TLR signalling is regulated by a TRAF2-dependent proteolysis mechanism in macrophages
Activation of Toll-like receptors induces inflammation, which is critical for defence against infection but can cause autoimmunity, and thus needs tight regulation. Here, the authors show that TRAF2 limits inflammatory responses downstream of these receptors by inducing degradation of IRF5 and c-Rel.
- Jin Jin
- , Yichuan Xiao
- & Shao-Cong Sun
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Article
| Open AccessFc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages
M2-polarized macrophages are generally considered anti-inflammatory, but whether polarization markers always reflect functional states remains debatable. Here the authors show that complexed IgG and TLR co-stimulation, observed in infections or rheumatoid arthritis, elicits an inflammatory response in M2 macrophages.
- Lisa T. C. Vogelpoel
- , Ivo S. Hansen
- & Jeroen den Dunnen
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Lysophospholipids secreted by splenic macrophages induce chemotherapy resistance via interference with the DNA damage response
It is known that mesenchymal stem cells contribute to chemotherapy resistance by secreting polyunsaturated fatty acids. Here the authors show that macrophages in the spleen secrete lysophosphatidylcholines and contribute to chemotherapy resistance by altering the tumour's DNA damage response.
- Julia M. Houthuijzen
- , Laura G. M. Daenen
- & Emile E Voest
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Protrusion force microscopy reveals oscillatory force generation and mechanosensing activity of human macrophage podosomes
Podosomes are actin-rich adhesion structures that show periodic oscillations in stiffness. Here, Labernadie et al.develop a method to measure the protrusion force and mechanosensing activity of individual podosomes, using an atomic force microscope and a flexible substrate membrane.
- Anna Labernadie
- , Anaïs Bouissou
- & Isabelle Maridonneau-Parini
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Article
| Open AccessCharacterizing the genetic basis of innate immune response in TLR4-activated human monocytes
Toll-like receptors (TLRs) are an essential component of innate immunity. Here, the authors identify expression quantitative trait loci that are unique to TLR4-stimulation and highlight genes that may have a role in innate immune response.
- Sarah Kim
- , Jessica Becker
- & Johannes Schumacher
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IRF8 inhibits C/EBPα activity to restrain mononuclear phagocyte progenitors from differentiating into neutrophils
The mechanisms mediating lineage restriction in haematopoietic cell differentiation are not well understood. Here the authors show when and how the transcription factor IRF8 inhibits neutrophil differentiation during the lineage selection of monocytes and dendritic cells.
- Daisuke Kurotaki
- , Michio Yamamoto
- & Tomohiko Tamura
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Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis
The protein Mincle can sense pathogens and molecules associated with cell death. Here the authors show that Mincle expressed in macrophages is a mediator of obesity-induced fibrosis and inflammation of adipose tissue, and that Mincle knockout mice are protected from diet-induced metabolic dysfunction.
- Miyako Tanaka
- , Kenji Ikeda
- & Yoshihiro Ogawa
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Article
| Open AccessToll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration
Inflammatory monocytes play an important role in host defense against infections. Here the authors provide insights into the mechanism behind the recruitment of inflammatory monocytes to sites of infection by demonstrating the involvement of Toll-like receptor 4 and MAIR-II immunoreceptors in this process.
- Naoya Totsuka
- , Yun-Gi Kim
- & Akira Shibuya
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Article
| Open AccessInvertebrate extracellular phagocyte traps show that chromatin is an ancient defence weapon
The process of controlled chromatin release from the nuclei of inflammatory cells to entrap and kill bacteria, termed ETosis, is important in innate immunity in vertebrates. Here the authors demonstrate that ETosis, mediated by hematocytes, also contributes to defence mechanisms in invertebrates.
- Calum T. Robb
- , Elisabeth A. Dyrynda
- & Valerie J. Smith
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Article
| Open AccessMiR-9 promotes microglial activation by targeting MCPIP1
MicroRNA-9 (miR-9) is known for its function in neurogenesis and axonal extension but its role in the immune responses in the brain is not fully understood. Here, Yao et al. show that miR-9 is involved in the activation of microglia, cells of the myeloid origin that are involved in immune surveillance in the brain.
- Honghong Yao
- , Rong Ma
- & Shilpa Buch
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Article
| Open AccessLong non-coding RNAs and enhancer RNAs regulate the lipopolysaccharide-induced inflammatory response in human monocytes
Long non-coding RNAs (lncRNAs) are important regulators of gene expression. Ilott et al. characterize changes in the expression of lncRNAs and enhancer RNAs during the inflammatory response in human monocytes and show that these RNAs can be involved in the regulation of the innate immunity.
- Nicholas E. Ilott
- , James A. Heward
- & Mark A. Lindsay
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The β-hydroxybutyrate receptor HCA2 activates a neuroprotective subset of macrophages
The ketone body β-hydroxybutyrate is produced in the liver in response to a ketogenic diet. Here, Rahman et al. show that β-hydroxybutyrate mediates the neuroprotective effect of a ketogenic diet by activating the HCA2receptor on a neuroprotective subset of macrophages.
- Mahbubur Rahman
- , Sajjad Muhammad
- & Markus Schwaninger
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Article |
MafB promotes atherosclerosis by inhibiting foam-cell apoptosis
In the early stages of atherosclerosis, macrophages in the vessel wall convert into foam cells, which promote the rise of atherosclerotic plaques. Here Hamada et al. show that the macrophage transcription factor MafB inhibits foam-cell apoptosis, and that its absence promotes atherosclerosis development in mice.
- Michito Hamada
- , Megumi Nakamura
- & Satoru Takahashi
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Article |
The TSC-mTOR pathway regulates macrophage polarization
Distinct macrophage phenotypes are associated with their polarization to a proinflammatory or alternative state, but it is not well understood how metabolic status affects this process. Here, Byles et al.demonstrate that the mTOR metabolic pathway regulates macrophage differentiation.
- Vanessa Byles
- , Anthony J. Covarrubias
- & Tiffany Horng
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Article
| Open AccessLRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition
Inflammasomes promote the maturation of inflammatory cytokines in response to signals associated with damage and infection, but it remains unclear how these signals are attenuated. Here, the authors show that the NLRP3 inflammasome is inhibited by LRRFIP2 through recruitment of the protein Flightless I.
- Jing Jin
- , Qian Yu
- & Xuetao Cao
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Article
| Open AccessBacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages
Bacterial infections can influence disease outcome in influenza infection; however, the mechanisms mediating these complex interactions remain unclear. Wang et al. reveal how infection with a component of the airway microbiota enhances survival during influenza infection via induction of anti-inflammatory macrophages.
- Jian Wang
- , Fengqi Li
- & Zhigang Tian
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Article |
Thymosin β4-sulfoxide attenuates inflammatory cell infiltration and promotes cardiac wound healing
Hydrogen peroxide attracts immune cells and induces wound inflammation. Evans et al. show that hydrogen peroxide also leads to the production of thymosin β4–sulfoxide in zebrafish wounds and in mouse hearts after myocardial infarction, where it acts as an anti-inflammatory factor that promotes wound healing.
- Mark A. Evans
- , Nicola Smart
- & Paul R. Riley
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Article |
Distinct bone marrow-derived and tissue-resident macrophage lineages proliferate at key stages during inflammation
Monocytes are recruited to sites of damage or infection where they differentiate into inflammatory macrophages. Here the authors demonstrate that, contrary to the prevailing model, these differentiated cells are able to proliferate at sites of inflammation.
- Luke C. Davies
- , Marcela Rosas
- & Philip R. Taylor
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MyD88 signalling in colonic mononuclear phagocytes drives colitis in IL-10-deficient mice
Mice lacking the anti-inflammatory cytokine IL-10 can develop colitis, which depends on inappropriate responses to commensal bacteria. Hoshiet al. now show that these responses are driven by colonic mononuclear phagocytes, providing insight to the initiating events, which may underlie inflammatory bowel disease.
- Namiko Hoshi
- , Dominik Schenten
- & Ruslan Medzhitov
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Macrophage VLDL receptor promotes PAFAH secretion in mother's milk and suppresses systemic inflammation in nursing neonates
Mother's milk contains a number of protective factors, such as the anti-inflammatory enzyme PAFAH. Here, Duet al. show that the VLDL receptor protects nursing newborns from systemic inflammation by maintaining secretion of PAFAH from maternal macrophages into mother's milk.
- Yang Du
- , Marie Yang
- & Yihong Wan