Single cell analysis of M. tuberculosis phenotype and macrophage lineages in the infected lung

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(9)

Published: July 22, 2021

In this study, we detail a novel approach that combines bacterial fitness fluorescent reporter strains with scRNA-seq to simultaneously acquire the host transcriptome, surface marker expression, and phenotype for each infected cell. This facilitates dissection of functional heterogeneity M. tuberculosis–infected alveolar (AMs) interstitial macrophages (IMs) in vivo. We identify clusters pro-inflammatory AMs associated stressed bacteria, addition three different populations IMs heterogeneous phenotypes. Finally, show main macrophage lung are epigenetically constrained their response infection, while inter-species comparison reveals most subsets conserved between mice humans. conceptual is readily transferable other infectious disease agents potential an increased understanding roles cell play during course infection.

Language: Английский

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A spatially resolved atlas of the human lung characterizes a gland-associated immune niche

Nature Genetics, Journal Year: 2022, Volume and Issue: 55(1), P. 66 - 77

Published: Dec. 21, 2022

Abstract Single-cell transcriptomics has allowed unprecedented resolution of cell types/states in the human lung, but their spatial context is less well defined. To (re)define tissue architecture lung and airways, we profiled five proximal-to-distal locations healthy lungs depth using multi-omic single cell/nuclei (queryable at lungcellatlas.org ). Using computational data integration analysis, extend beyond suspension paradigm discover macro micro-anatomical compartments including previously unannotated types epithelial, vascular, stromal nerve bundle micro-environments. We identify implicate peribronchial fibroblasts disease. Importantly, validate a survival niche for IgA plasma cells airway submucosal glands (SMG). show that gland epithelial recruit B cells, promote longevity antibody secretion locally through expression CCL28, APRIL IL-6. This new ‘gland-associated immune niche’ implications respiratory health.

Language: Английский

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Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth

The Journal of Experimental Medicine, Journal Year: 2021, Volume and Issue: 218(10)

Published: Aug. 25, 2021

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice profile pulmonary expression, which we detected in both cells, including group 2 innate lymphoid γδ T as well AT2s. AMs were unaffected constitutive deletion hematopoietic Csf2 basophil depletion. Instead, AT2 lineage-specific inducible revealed the nonredundant function AT2-derived instructing AM fate, establishing postnatal compartment, maintaining adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce expression support proliferation differentiation fetal monocytes contemporaneously seeding tissue, persists into adulthood, when epithelial restricted

Language: Английский

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Tissue-Resident Immune Cells in Humans

Annual Review of Immunology, Journal Year: 2022, Volume and Issue: 40(1), P. 195 - 220

Published: Jan. 19, 2022

Tissue-resident immune cells span both myeloid and lymphoid cell lineages, have been found in multiple human tissues, play integral roles at all stages of the response, from maintaining homeostasis to responding infectious challenges resolution inflammation tissue repair. In humans, studying responses tissues is challenging, although recent advances sampling high-dimensional profiling provided new insights into ontogeny, maintenance, functional role tissue-resident cells. Each contains a specific complement resident Moreover, for each lineage share core properties, along with tissue-specific adaptations. Here we propose five-point checklist defining types humans describe currently known features cells, their mechanisms development, putative within various organs. We also consider these aspects context future studies therapeutics.

Language: Английский

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Regulatory T cell and macrophage crosstalk in acute lung injury: future perspectives

Cell Death Discovery, Journal Year: 2023, Volume and Issue: 9(1)

Published: Jan. 16, 2023

Abstract Acute lung injury (ALI) describes the to endothelial cells in lungs and associated vessels due various factors. Furthermore, ALI accompanied by inflammation thrombosis has been reported as a common complication of SARS-COV-2 infection. It is widely accepted that cytokine storm are main causes ALI. Two classical anti-inflammatory cell types, regulatory T (Tregs) M2 macrophages, theoretically capable resisting uncontrolled inflammation. Recent studies have indicated possible crosstalk between Tregs macrophages involving their mutual activation. In this review, we discuss current findings related pathogenesis role macrophages. particular, review molecular mechanisms underlying pathogenesis. Understanding will provide potential targets for treating

Language: Английский

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Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities

Biomarker Research, Journal Year: 2024, Volume and Issue: 12(1)

Published: Jan. 7, 2024

Abstract Tumor-associated macrophages (TAMs) are a heterogeneous population that play diverse functions in tumors. Their identity is determined not only by intrinsic factors, such as origins and transcription but also external signals from the tumor microenvironment (TME), inflammatory metabolic reprogramming. Metabolic reprogramming has rendered TAM to exhibit spectrum of activities ranging pro-tumorigenic anti-tumorigenic, closely associated with progression clinical prognosis. This review implicates diversity phenotypes functions, how this heterogeneity been re-evaluated advent single-cell technologies, impact TME on TAMs. We current therapies targeting metabolism offer new insights for TAM-dependent anti-tumor immunotherapy focusing critical role different programs

Language: Английский

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Classical monocyte ontogeny dictates their functions and fates as tissue macrophages

Immunity, Journal Year: 2024, Volume and Issue: 57(6), P. 1225 - 1242.e6

Published: May 14, 2024

Language: Английский

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How macrophage heterogeneity affects tuberculosis disease and therapy

Nature reviews. Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 7, 2025

Language: Английский

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Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: March 7, 2025

Abstract Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in defense, surveillance, and homeostasis. This review systematically discusses types of hematopoietic progenitors that give rise macrophages, including primitive progenitors, erythro-myeloid stem cells. These have distinct genetic backgrounds developmental processes. Accordingly, macrophages exhibit complex diverse functions body, phagocytosis clearance cellular debris, antigen presentation, response, regulation inflammation cytokine production, tissue remodeling repair, multi-level regulatory signaling pathways/crosstalk involved homeostasis physiology. Besides, tumor-associated a key component TME, exhibiting both anti-tumor pro-tumor properties. Furthermore, functional status is closely linked development various diseases, cancer, autoimmune disorders, cardiovascular disease, neurodegenerative metabolic conditions, trauma. Targeting has emerged as promising therapeutic strategy these contexts. Clinical trials macrophage-based targeted drugs, immunotherapies, nanoparticle-based therapy were comprehensively summarized. Potential challenges future directions targeting also been discussed. Overall, our highlights significance this versatile cell human health which expected inform research clinical practice.

Language: Английский

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The Role of Macrophages in the Pathogenesis of SARS-CoV-2-Associated Acute Respiratory Distress Syndrome

Frontiers in Immunology, Journal Year: 2021, Volume and Issue: 12

Published: May 10, 2021

Macrophages are cells that mediate both innate and adaptive immunity reactions, playing a major role in physiological pathological processes. Systemic SARS-CoV-2-associated complications include acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation syndrome, edema, pneumonia. These predominantly effects of massive macrophage activation collectively can be defined as syndrome. In this review we focus on the macrophages COVID-19, pathogenesis new coronavirus infection, especially cases complicated by ARDS, largely depends phenotypes functionalities. We describe participation monocytes, monocyte-derived resident lung ARDS discuss possible utility cell therapies for its treatment, notably use reprogrammed with stable pro- or anti-inflammatory phenotypes.

Language: Английский

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