Biology of lung macrophages in health and disease

Immunity, Journal Year: 2022, Volume and Issue: 55(9), P. 1564 - 1580

Published: Sept. 1, 2022

Language: Английский

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Tissue-specific macrophages: how they develop and choreograph tissue biology

Nature reviews. Immunology, Journal Year: 2023, Volume and Issue: 23(9), P. 563 - 579

Published: March 15, 2023

Macrophages are innate immune cells that form a 3D network in all our tissues, where they phagocytose dying and cell debris, complexes, bacteria other waste products. Simultaneously, produce growth factors signalling molecules — such activities not only promote host protection response to invading microorganisms but also crucial for organ development homeostasis. There is mounting evidence of macrophages orchestrating fundamental physiological processes, as blood vessel formation, adipogenesis, metabolism central peripheral neuronal function. In parallel, novel methodologies have led the characterization tissue-specific macrophages, with distinct subpopulations these showing different developmental trajectories, transcriptional programmes life cycles. Here, we summarize growing knowledge macrophage diversity how subsets orchestrate tissue We further interrelate ontogeny their core functions across is, events within niche may control functionality during development, homeostasis ageing. Finally, highlight open questions will need be addressed by future studies better understand subsets. important immunity infections clearing products from maintain health regulating metabolism, many biological processes. Elvira Mass co-workers discuss populations found throughout body, highlighting shared unique aspects functions.

Language: Английский

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M1/M2 macrophages and their overlaps – myth or reality?

Clinical Science, Journal Year: 2023, Volume and Issue: 137(15), P. 1067 - 1093

Published: Aug. 1, 2023

Abstract Macrophages represent heterogeneous cell population with important roles in defence mechanisms and homoeostasis. Tissue macrophages from diverse anatomical locations adopt distinct activation states. M1 M2 are two polarized forms of mononuclear phagocyte vitro differentiation phenotypic patterns functional properties, but vivo, there is a wide range different macrophage phenotypes between depending on the microenvironment natural signals they receive. In human infections, pathogens use strategies to combat these include shaping polarization towards one or another phenotype. infiltrating tumours can affect patient’s prognosis. have been shown promote tumour growth, while provide both tumour-promoting anti-tumour properties. autoimmune diseases, prolonged activation, as well altered function contribute their onset activity. atherosclerotic lesions, expressing profiles detected potential factors affecting occurrence cardiovascular diseases. allergic inflammation, T2 cytokines drive profiles, which airway inflammation remodelling. transplantations seem acute rejection, fibrosis graft. The view pro-inflammatory suppressing seems be an oversimplification because cells exploit very high level plasticity large scale immunophenotypes overlapping this respect, it would more precise describe M1-like M2-like.

Language: Английский

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Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(19)

Published: Oct. 1, 2023

Alveolar macrophages (AMs) are the sentinel cells of alveolar space, maintaining homeostasis, fending off pathogens, and controlling lung inflammation. During acute injury, AMs orchestrate initiation resolution inflammation in order to ultimately restore homeostasis. This central role makes attractive targets for therapeutic interventions. Single-cell RNA-Seq spatial omics approaches, together with methodological advances such as generation human from pluripotent stem cells, have increased understanding ontogeny, function, plasticity during infectious sterile inflammation, which could move field closer clinical application. However, proresolution phenotypes might conflict proinflammatory antibacterial responses. Therefore, targeting at vulnerable time points over course injury harbor risk serious side effects, loss host defense capacity. Thus, identification key signaling hubs that determine functional fate decisions is utmost importance harness their potential.

Language: Английский

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An Inhalable Hybrid Biomimetic Nanoplatform for Sequential Drug Release and Remodeling Lung Immune Homeostasis in Acute Lung Injury Treatment

ACS Nano, Journal Year: 2023, Volume and Issue: 17(12), P. 11626 - 11644

Published: June 7, 2023

Interactions of lung macrophages and recruited neutrophils with the microenvironment continuously aggravate dysregulation inflammation in pathogenesis acute injury (ALI) or respiratory distress syndrome (ARDS). Either modulating destroying neutrophil counts cannot guarantee a satisfactory outcome ARDS treatment. Aimed at inhibiting coordinated action hyper-inflammatory condition, an inhalable biomimetic sequential drug-releasing nanoplatform was developed for combinatorial treatment ALI. The (termed D-SEL) made by conjugating DNase I, as outer cleavable arms, to serum exosomal liposomal hybrid nanocarrier SEL) via matrix metalloproteinase 9 (MMP-9)-cleavable peptide then encapsulating methylprednisolone sodium succinate (MPS). In lipopolysaccharide (LPS) induced ALI mice, MPS/D-SEL moved through muco-obstructive airways retained alveoli over 24 h postinhalation. I released from first after responding MMP-9, resulting inner SEL core exposure, which precisely delivered MPS into promoting M2 macrophage polarization. Local sustained release degraded dysregulated extracellular traps (NETs) suppressed activation mucus plugging microenvironment, turn amplified polarization efficiency. Such dual-stage drug behavior facilitated down-regulation pro-inflammatory cytokines but anti-inflammatory cytokine production remodeling immune homeostasis, ultimately tissue repair. This work presents versatile local pulmonary delivery dual-drug therapeutics displays potential inflammation.

Language: Английский

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SARS-CoV-2 viral persistence in lung alveolar macrophages is controlled by IFN-γ and NK cells

Nature Immunology, Journal Year: 2023, Volume and Issue: 24(12), P. 2068 - 2079

Published: Nov. 2, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA generally becomes undetectable in upper airways after a few days or weeks postinfection. Here we used model of viral infection macaques to address whether SARS-CoV-2 persists the body and which mechanisms regulate its persistence. Replication-competent virus was detected bronchioalveolar lavage (BAL) macrophages beyond 6 months Viral propagation BAL occurred from cell inhibited by interferon-γ (IFN-γ). IFN-γ production strongest NKG2r+CD8+ T cells NKG2Alo natural killer (NK) further increased NK spike protein stimulation. However, impaired with persisting virus. Moreover, also enhanced expression major histocompatibility complex (MHC)-E on macrophages, possibly inhibiting cell-mediated killing. Macaques less mounted adaptive that escaped MHC-E-dependent inhibition. Our findings reveal an interplay between regulated persistence mediated IFN-γ.

Language: Английский

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Immune mechanisms of granuloma formation in sarcoidosis and tuberculosis

Journal of Clinical Investigation, Journal Year: 2024, Volume and Issue: 134(1)

Published: Jan. 1, 2024

Sarcoidosis is a complex immune-mediated disease characterized by clusters of immune cells called granulomas. Despite major steps in understanding the cause this disease, many questions remain. In Review, we perform mechanistic interrogation activities that contribute to granuloma formation sarcoidosis and compare these processes with its closest mimic, tuberculosis, highlighting shared divergent activities. We examine how Mycobacterium tuberculosis sensed system; initiated, formed, perpetuated compared sarcoidosis; role innate adaptive shaping processes. Finally, draw findings together around several recent high-resolution studies situ utilized latest advances single-cell technology combined spatial methods analyze plausible mechanisms. conclude an overall view sarcoidosis.

Language: Английский

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Coordinated chemokine expression defines macrophage subsets across tissues

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(6), P. 1110 - 1122

Published: May 2, 2024

Language: Английский

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Spatial transcriptomics identifies molecular niche dysregulation associated with distal lung remodeling in pulmonary fibrosis

Nature Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Abstract Large-scale changes in the structure and cellular makeup of distal lung are a hallmark pulmonary fibrosis (PF), but spatial contexts that contribute to disease pathogenesis have remained uncertain. Using image-based transcriptomics, we analyzed gene expression 1.6 million cells from 35 unique lungs. Through complementary cell-based innovative cell-agnostic analyses, characterized localization PF-emergent cell types, established molecular basis classical PF histopathologic features identified diversity distinct molecularly defined niches control machine learning trajectory analysis segment rank airspaces on gradient remodeling severity, compositional associated with progressive pathology, beginning alveolar epithelial dysregulation culminating macrophage polarization. Together, these results provide unique, spatially resolved view establish methods could be applied other transcriptomic studies.

Language: Английский

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Trained immunity of alveolar macrophages requires metabolic rewiring and type 1 interferon signaling

Mucosal Immunology, Journal Year: 2022, Volume and Issue: 15(5), P. 896 - 907

Published: July 18, 2022

Environmental microbial triggers shape the development and functionality of immune system. Alveolar macrophages (AMs), tissue-resident lungs, are in constant direct contact with inhaled particles microbes. Such exposures likely impact AM reactivity to subsequent challenges by immunological imprinting mechanisms referred as trained immunity. Here, we investigated whether a ubiquitous compound has potential induce training vivo. We discovered that intranasal exposure ambient amounts lipopolysaccharide (LPS) induced pronounced memory response, characterized enhanced upon pneumococcal challenge. Exploring mechanistic basis training, identified critical role type 1 interferon signaling found inhibition fatty acid oxidation glutaminolysis significantly attenuated effect. Notably, adoptive transfer AMs resulted increased bacterial loads tissue damage infection. In contrast, pre-exposure LPS promoted clearance, highlighting complexity stimulus-induced responses, which involve multiple cell types may depend on local metabolic environment. Collectively, our findings demonstrate profound pulmonary reveal tissue-specific features

Language: Английский

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