Myeloid cells are a significant proportion of leukocytes within tissues, comprising granulocytes, monocytes, dendritic cells, and macrophages. With the identification of various myeloid cells that ...perform separate but complementary functions during homeostasis and disease, our understanding of tissue myeloid cells has evolved significantly. Exciting findings from transcriptomics profiling and fate-mapping mouse models have facilitated the identification of their developmental origins, maturation, and tissue-specific specializations. This review highlights the current understanding of tissue myeloid cells and the contributing factors of functional heterogeneity to better comprehend the complex and dynamic immune interactions within the healthy or inflamed tissue. Specifically, we discuss the new understanding of the contributions of granulocyte-monocyte progenitor-derived phagocytes to tissue myeloid cell heterogeneity as well as the impact of niche-specific factors on monocyte and neutrophil phenotype and function. Lastly, we explore the developing paradigm of myeloid cell heterogeneity during inflammation and disease.
Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue ...immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2+ lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.
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•scRNA-seq reveals a dynamic adipose tissue immune cell atlas in mice and humans•Massive induction of a conserved LAM program during obesity•The lipid receptor Trem2 is essential for LAM protective functions•LAMs counteract inflammation, adipocyte hypertrophy, and metabolic disease
A single-cell atlas of human and mouse adipose tissue uncovers protective lipid-associated macrophages (LAMs), which perform lipid uptake and metabolism to prevent adipocyte hypertrophy, inflammation, and systemic metabolic dysregulation in a Trem2 signaling-dependent manner.
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•Anammox was enriched in carriers to enhance ability against adverse environment.•As influent TN was 3000mg/L, effluent TN was below 20mg/L with TN removal of 95%.•The ratio of ...NO3−:NH4+ fell below 0.1 in Anammox process treating real leachate.•TB-EPS of biofilm and floccule were 46% and 28%, respectively, helped form biofilm.•Anammox gene ratio of biofilm increased to 13.28%, yet floccule decreased to 3.88%.
High levels of organics negatively affect Anammox for treating landfill leachate. To enhance the ability of Anammox to survive against adverse environments, a lab-scale two-stage Anammox system using a Sequencing Biofilm Batch Reactor was applied to treat mature landfill leachate under 35°C. Over 107days, with influent total nitrogen (TN) and chemical oxygen demand (COD) concentrations of 3000±100 and 3000±100mg/L, effluent TN was below 20mg/L. For extracellular polymeric substance (EPS) of Anammox, slime-EPS and loosely-bound-EPS of floccules were both higher than biofilm, while tight-bound-EPS of biofilm was significantly higher, contributing to biofilm formation. Quantitative microbial analysis showed that as influent COD increased, Anammox gene ratios of biofilm increased from 1.34% to 13.28%; the gene ratios of floccule first increased, then decreased to 3.88%. This indicated that Anammox and heterotrophic bacteria could coexist because of the biofilm, leading to stable nitrogen removal performance, even when organics were present.
Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary-gland function, their diversity has not been fully addressed. By exploiting ...high-resolution three-dimensional imaging and flow cytometry, we identified a unique population of tissue-resident ductal macrophages that form a contiguous network between the luminal and basal layers of the epithelial tree throughout postnatal development. Ductal macrophages are long lived and constantly survey the epithelium through dendrite movement, revealed via advanced intravital imaging. Although initially originating from embryonic precursors, ductal macrophages derive from circulating monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, when they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, ductal macrophages strongly resemble mammary tumour macrophages and form a network that pervades the tumour. Thus, the mammary epithelium programs specialized resident macrophages in both physiological and tumorigenic contexts.
This study presents a modified compensating observer control strategy for nonlinear multi-agent systems affected by unknown hysteresis signal loops. Compared to conventional high-gain observers, this ...approach introduces a novel compensation signal, effectively reducing the tracking error of traditional observers. Then, by utilizing a backstepping method, an adaptive output feedback controller is designed, such that the tracking error converges to the small neighborhood around the origin. Simulation experiments with and without the compensation term demonstrate that this control strategy can effectively reduce error, but it increases input chattering to some extent.
Brain macrophage populations include parenchymal microglia, border-associated macrophages, and recruited monocyte-derived cells; together, they control brain development and homeostasis but are also ...implicated in aging pathogenesis and neurodegeneration. The phenotypes, localization, and functions of each population in different contexts have yet to be resolved. We generated a murine brain myeloid scRNA-seq integration to systematically delineate brain macrophage populations. We show that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer’s disease models actually comprises two ontogenetically and functionally distinct cell lineages: embryonically derived triggering receptor expressed on myeloid cells 2 (TREM2)-dependent DAM expressing a neuroprotective signature and monocyte-derived TREM2-expressing disease inflammatory macrophages (DIMs) accumulating in the brain during aging. These two distinct populations appear to also be conserved in the human brain. Herein, we generate an ontogeny-resolved model of brain myeloid cell heterogeneity in development, homeostasis, and disease and identify cellular targets for the treatment of neurodegeneration.
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•M-Verse as a global cross-comparison of developing and adult murine brain macrophages•DAM correspond to a fetal-like reprogramming similar to Youth-Associated Microglia•DIMs appear during aging and increase in neurodegenerative diseases•DAM are embryonic derived, whereas DIMs are TREM2-independent monocyte derived
Through 6 scRNA-seq brain dataset integration, the authors generated a myeloid map called M-Verse to delineate macrophage population heterogeneity. M-Verse revealed two distinct macrophage populations expressing published disease-associated microglia (DAM) signature: embryonically derived TREM2-dependent DAM and monocyte-derived TREM2-independent disease inflammatory macrophages (DIMs).
The percentage of macrophage subpopulations based on their origins in the adult cochlea remains unclear. This study aimed to elucidate the origins of cochlear macrophages during the onset phase and ...development of auditory function. We used three types of mice: wildtype ICR mice, colony-stimulating factor 1 receptor (Csf1r)-deficient mice, and Ms4a3Cre-Rosa tdTomato (Ms4a3
) transgenic mice. Macrophages were labeled with ionized calcium-binding adapter molecule 1 (Iba1), which is specific to more mature macrophages, and CD11b, which is specific to monocyte lineage. We investigated the spatial and temporal distribution patterns of resident macrophages in the cochlea during the postnatal and early adult stages. During the adult stages, the rate of monocytes recruited from the systemic circulation increased; moreover, Iba1
/CD11b
cochlear macrophages gradually decreased with age. Fate mapping of monocytes using Ms4a3
transgenic mice revealed an increased proportion of bone marrow-derived cochlear macrophages in the adult stage. Contrastingly, the proportion of yolk sac- and fetal liver-derived tissue-resident macrophages decreased steadily with age. This heterogeneity could be attributed to differences in environmental niches within the tissue or at the sub-tissue levels. Future studies should investigate the role of cochlear macrophages in homeostasis, inflammation, and other diseases, including infection, autoimmune, and metabolic diseases.
During inflammation, Ly6C
monocytes are rapidly mobilized from the bone marrow (BM) and are recruited into inflamed tissues, where they undergo monocyte-to-phagocyte transition (MTPT). The in vivo ...developmental trajectories of the MTPT and the contribution of individual cytokines to this process remain unclear. Here, we used a murine model of neuroinflammation to investigate how granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-γ (IFNγ), two type 1 cytokines, controlled MTPT. Using genetic fate mapping, gene targeting and high-dimensional single-cell multiomics analyses, we found that IFNγ was essential for the gradual acquisition of a mature inflammatory phagocyte phenotype in Ly6C
monocytes, while GM-CSF was required to license interleukin-1β (IL-1β) production, phagocytosis and oxidative burst. These results suggest that the proinflammatory cytokine environment guided MTPT trajectories in the inflamed central nervous system (CNS) and indicated that GM-CSF was the most prominent target for the disarming of monocyte progenies during neuroinflammation.
Cisplatin is one of the most effective chemotherapeutic drugs used in the treatment of HCC, but many patients will ultimately relapse with cisplatin-resistant disease. Used in combination with ...cisplatin, resveratrol has synergistic effect of increasing chemosensitivity of cisplatin in various cancer cells. However, the mechanisms of resveratrol enhancing cisplatininduced toxicity have not been well characterized. Our study showed that resveratrol enhances cisplatin toxicity in human hepatoma cells via an apoptosis-dependent mechanism. Further studies reveal that resveratrol decreases the absorption of glutamine and glutathione content by reducing the expression of glutamine transporter ASCT2. Flow cytometric analyses demonstrate that resveratrol and cisplatin combined treatment leads to a significant increase in ROS production compared to resveratrol or cisplatin treated hepatoma cells alone. Phosphorylated H2AX (γH2AX) foci assay demonstrate that both resveratrol and cisplatin treatment result in a significant increase of γH2AX foci in hepatoma cells, and the resveratrol and cisplatin combined treatment results in much more γH2AX foci formation than either resveratrol or cisplatin treatment alone. Furthermore, our studies show that over-expression of ASCT2 can attenuate cisplatin-induced ROS production, γH2AX foci formation and apoptosis in human hepatoma cells. Collectively, our studies suggest resveratrol may sensitize human hepatoma cells to cisplatin chemotherapy via glutamine metabolism inhibition. BMB Reports 2018; 51(9): 474-479.
Abstract
Solar flares can release coronal magnetic energy explosively and may impact the safety of near-Earth space environments. Their structures and properties on the macroscale have been ...interpreted successfully by the generally accepted 2D standard model, invoking magnetic reconnection theory as the key energy conversion mechanism. Nevertheless, some momentous dynamical features as discovered by recent high-resolution observations remain elusive. Here, we report a self-consistent high-resolution 3D magnetohydrodynamical simulation of turbulent magnetic reconnection within a flare current sheet. It is found that fragmented current patches of different scales are spontaneously generated with a well-developed turbulence spectrum at the current sheet, as well as at the flare loop-top region. The close coupling of tearing mode and Kelvin–Helmholtz instabilities plays a critical role in developing turbulent reconnection and in forming dynamical structures with synthetic observables in good agreement with realistic observations. The sophisticated modeling makes a paradigm shift from the traditional to a 3D turbulent reconnection model unifying flare dynamical structures of different scales.
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