The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Austermann, Judith; Roth, Johannes; Barczyk-Kahlert, Katarzyna

doi:10.3390/cells11121979

Cited by 76 publications

(57 citation statements)

References 170 publications

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“…Of them, inflammatory monocytes play an important role as these cells express toll-like receptors (TLRs) and scavenger receptors that mediate the recognition of pathogen-associated molecular patterns and damage-associated molecular patterns. As a consequence, inflammatory monocytes infiltrate tissues where they can differentiate into macrophages and release effector molecules such as cytokines, myeloperoxidase, and superoxide, thereby initiating inflammation [ 55 , 56 ].…”

Section: Resultsmentioning

confidence: 99%

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

et al. 2022

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Nanomedicines based on inorganic nanoparticles have grown in the last decades due to the nanosystems’ versatility in the coating, tuneability, and physical and chemical properties. Nonetheless, concerns have been raised regarding the immunotropic profile of nanoparticles and how metallic nanoparticles affect the immune system. Cationic polymer nanoparticles are widely used for cell transfection and proved to exert an adjuvant immunomodulatory effect that improves the efficiency of conventional vaccines against infection or cancer. Likewise, gold nanoparticles (AuNPs) also exhibit diverse effects on immune response depending on size or coatings. Photothermal or photodynamic therapy, radiosensitization, and drug or gene delivery systems take advantage of the unique properties of AuNPs to deeply modify the tumoral ecosystem. However, the collective effects that AuNPs combined with cationic polymers might exert on their own in the tumor immunological microenvironment remain elusive. The purpose of this study was to analyze the triple-negative breast tumor immunological microenvironment upon intratumoral injection of polyethyleneimine (PEI)–AuNP nanocomposites (named AuPEI) and elucidate how it might affect future immunotherapeutic approaches based on this nanosystem. AuPEI nanocomposites were synthesized through a one-pot synthesis method with PEI as both a reducing and capping agent, resulting in fractal assemblies of about 10 nm AuNPs. AuPEI induced an inflammatory profile in vitro in the mouse macrophage-like cells RAW264.7 as determined by the secretion of TNF-α and CCL5 while the immunosuppressor IL-10 was not increased. However, in vivo in the mouse breast MET-1 tumor model, AuPEI nanocomposites shifted the immunological tumor microenvironment toward an M2 phenotype with an immunosuppressive profile as determined by the infiltration of PD-1-positive lymphocytes. This dichotomy in AuPEI nanocomposites in vitro and in vivo might be attributed to the highly complex tumor microenvironment and highlights the importance of testing the immunogenicity of nanomaterials in vitro and more importantly in vivo in relevant immunocompetent mouse tumor models to better elucidate any adverse or unexpected effect.

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Section: Resultsmentioning

confidence: 99%

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

et al. 2022

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“…The C3 + monocytes with anti-inflammatory traits were probably induced by persistent stimulation of reparative mediators and attempted to negatively regulate inflammation within plaques. 67 Unlike proinflammatory EREG + monocytes that differentiated into IGF1 + and HS3ST2 + macrophages, C3 + monocytes may be precursor of M2-like macrophages. 3,68 Macrophage plasticity, polarization, and commensurate functional phenotypes were critical for atherosclerotic progression and cerebrovascular events.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events

Tan,

Liang,

Yang

et al. 2023

ATVB

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BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients’ carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted. RESULTS: Compared with peripheral blood mononuclear cells, 3 plaque-specific T-cell subsets exhibiting proatherogenic features of both activation and exhaustion were identified. Strikingly, usually antiatherogenic, CD4 + FOXP3 + regulatory T cells from plaques of patients with symptomatic disease acquired proinflammatory properties by probably converting to T helper 17 and T helper 9 cells, while CD4 + NR4A1 + /C0 and CD8 + SLC4A10 + T cells related to cerebrovascular events possessed atherogenic attributes including proinflammation, polarization, and exhaustion. In addition, monocyte-macrophage dynamics dominated innate immune response. Two plaque-specific monocyte subsets performed diametrically opposed functions, EREG + monocytes promoted cerebrovascular events while C3 + monocytes are anti-inflammatory. Similarly, IGF1 + and HS3ST2 + macrophages with classical proinflammatory M1 macrophage features were annotated and contributed to cerebrovascular events. Moreover, SULF1 + (sulfatase-1) endothelial cells were also found to participate in cerebrovascular events through affecting plaque vulnerability. CONCLUSIONS: This compendium of single-cell transcriptome data provides valuable insights into the cellular heterogeneity of the atherosclerotic microenvironment and the development of more precise cardiovascular immunotherapies.

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“…Finally, this leads to CTLA-4 upregulation that competes with CD28 for CD80/86 binding, resulting in the termination of T-cell stimulation. Furthermore, CD86 is a marker for APC activation ( 47 ) and CD86 receptor downregulation can lead to an anti-inflammatory and immune-regulatory phenotype ( 48 ) and may indicate the presence of a wound healing phase following ablation therapy. With regard to CD200R+ monocytes, we detected decreased fractions following treatment with IBT, but no relevant changes following RFA.…”

Section: Discussionmentioning

confidence: 99%

Early monocyte response following local ablation in hepatocellular carcinoma

et al. 2022

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Local ablative therapies are established treatment modalities in the treatment of early- and intermediate-stage hepatocellular carcinoma (HCC). Systemic effects of local ablation on circulating immune cells may contribute to patients’ response. Depending on their activation, myeloid cells are able to trigger HCC progression as well as to support anti-tumor immunity. Certain priming of monocytes may already occur while still in the circulation. By using flow cytometry, we analyzed peripheral blood monocyte cell populations from a prospective clinical trial cohort of 21 HCC patients following interstitial brachytherapy (IBT) or radiofrequency ablation (RFA) and investigated alterations in the composition of monocyte subpopulations and monocytic myeloid-derived suppressor cells (mMDSCs) as well as receptors involved in orchestrating monocyte function. We discovered that mMDSC levels increased following both IBT and RFA in virtually all patients. Furthermore, we identified varying alterations in the level of monocyte subpopulations following radiation compared to RFA. (A) Liquid biopsy liquid biopsy of circulating monocytes in the future may provide information on the inflammatory response towards local ablation as part of an orchestrated immune response.

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The Good and the Bad: Monocytes’ and Macrophages’ Diverse Functions in Inflammation

Cited by 76 publications

References 170 publications

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

Cationic Polyethyleneimine (PEI)–Gold Nanocomposites Modulate Macrophage Activation and Reprogram Mouse Breast Triple-Negative MET-1 Tumor Immunological Microenvironment

Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events

Early monocyte response following local ablation in hepatocellular carcinoma

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