Tumor cell efferocytosis in monocyte derived macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE184317 | GEO | 2022/09/01
REPOSITORIES: GEO
Similar Datasets
Project description:Inflammation is a physiopathological process triggered by infection or tissue damage. Immune system initiates coordinated sequential steps in response to these danger signals. Once the threat has been contained inflammation has to be subsequently shut down. Inflammation resolution is initiated by the reprogramming of pro-inflammatory macrophages toward a pro-resolving profile. This reprogramming is induced in particular by the non-phlogistic engulfment of apoptotic cells, mostly apoptotic neutrophils, a process called efferocytosis. As a matter of fact, macrophages are an essential linchpin regulating both inflammation triggering and sustaining and inflammation resolution. This duality can be achieved through the tremendous plasticity of these innate immune cells. Indeed, depending on microenvironmental signals (cytokines, efferocytosis, growth factors…) macrophages can adopt numerous diverse and sometimes antagonistic phenotypes. The mechanisms governing these transitions remain relatively scattered especially in human. With this project we propose to explore the mechanisms involved in human macrophage reprogramming toward a pro-resolving profile after efferocytosis. The stakes are high due to the estimated prevalence of chronic inflammatory diseases in Western society is 5 to 7%. Chronic inflammation is a burden to patient due to life-long debilitating illness and increased mortality and is also a burden to society due to high costs for therapy and care. Finding new therapies to limit chronic inflammation establishment and persistence is thus a highly valuable goal.
2021-12-01 | E-MTAB-8885 | biostudies-arrayexpress
Project description:scRNAseq profiling of FACS-sorted myeloid enriched (DAPI-CD45+Ly6G- CD3e-CD11b+ and/or CD11c+) and lymphoid enriched (DAPI-CD45+Ly6G- CD3e+) fractions purified from murine lungs bearing KP-GFP tumor lesions (28 days after tumor delivery intravenously) isolated from Trem2+/+ and Trem2-/- animals
2022-09-01 | GSE184304 | GEO
Project description:scRNAseq profiling of FACS-sorted Trem2 +/+ (CD45.2+) and Trem2 -/- (CD45.1+) myeloid enriched (DAPI-CD45+Ly6G- CD3e-CD11b+ and/or CD11c+) fractions purified from KP-GFP bearing lungs (21 days after tumor delivery intravenously) isolated from mixed bone marrow chimeric mice.
2022-09-01 | GSE184309 | GEO
Project description:Recently it was shown that circulating Ly6C(+) monocytes traffic from tissue to the draining lymph nodes (LNs) with minimal alteration in their overall phenotype. Furthermore, in the steady state, Ly6C(+) monocytes are as abundant as classical dendritic cells (DCs) within the draining LNs, and even more abundant during inflammation. However, little is known about the functional roles of constitutively trafficking Ly6C(+) monocytes. In this study we investigated whether Ly6C(+) monocytes can efferocytose (acquire dying cells) and cross-present cell-associated antigen, a functional property particularly attributed to Batf3(+) DCs. We demonstrated that Ly6C(+) monocytes intrinsically efferocytose and cross-present cell-associated antigen to CD8(+) T cells. In addition, efferocytosis was enhanced upon direct activation of the Ly6C(+) monocytes through its corresponding TLRs, TLR4 and TLR7. However, only ligation of TLR7, and not TLR4, enhanced cross-presentation by Ly6C(+) monocytes. Overall, this study outlines two functional roles, among others, that Ly6C(+) monocytes have during an adaptive immune response.
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Project description:Klebsiella pneumoniae (KP) are extracellular Gram-negative bacteria that cause infections in lower respiratory and urinary tract, and bloodstream. STAT1 is a master transcription factor that acts to maintain T-cell quiescence under homeostatic conditions. Although STAT1 helps defend against systemic spread of acute KP intrapulmonary infection, whether STAT1 regulation of T-cell homeostasis impacts pulmonary host defense during acute bacterial infection and injury is less clear. Using a clinical KP respiratory isolate and a pneumonia mouse model, we found STAT1-deficiency led to an early neutrophil-dominant transcriptional profile and neutrophil-recruitment in the lung preceding widespread bacterial dissemination and lung injury development. Yet, myeloid cell STAT1 was dispensable for control of KP proliferation and dissemination, as myeloid cell-specific STAT1-deficient (LysMCre/WT;Stat1fl/fl) mice showed similar bacterial burden in lung, liver, and kidney as WT littermates. Surprisingly, IL-17 producing CD4+ T-cells infiltrated Stat1-/- mice lungs early during KP infection. Increase in Th17-cells in the lung was not due to preexisting immunity against KP and were consistent with circulating rather than tissue-resident CD4+ T-cells. However, blocking global IL17 signaling with anti-IL17-RC administration led to increased proliferation and dissemination of KP, suggesting IL17 provided by other innate immune cells is essential in defense against KP. Contrastingly, depletion of CD4+ T-cells reduced Stat1-/- mice lung bacterial burden indicating early CD4+ T-cell activation in the setting of global STAT1-deficiency is pathogenic. Altogether, our findings suggest STAT1 employs myeloid cell-extrinsic mechanisms to regulate neutrophil responses and provide protection against invasive KP by restricting non-specific CD4+ T-cell activation and immunopathology in the lung.
2024-01-10 | GSE251767 | GEO
Project description:To investigate the function of LRIG11 in regulating the differentiation of polyclonal CD8 tumor infiltrating T cells during the response to B16melanoma. And, To investigate the function of LRIG1 in regulating the activaiton of ovalbumin specific OT1 CD8+ T cells during the response to B16 tumor stably expresss ovalbumin as surrogate tumor antigen.
2024-01-02 | GSE245841 | GEO
Project description:YAP depletion in the KP tumor system results in smaller tumors and delayed tumor latency. We used microarrays to investigate changes in global gene expression due to YAP1 loss in KP tumors
2018-03-01 | GSE109920 | GEO
Project description:BACKGROUND:Galectin-3 is a 32?kDa protein secreted by macrophages involved in processes such as cell activation, chemotaxis and phagocytosis. Galectin-3 has previously been shown to improve the ability of airway macrophages to ingest apoptotic cells (efferocytosis) in chronic obstructive pulmonary disease (COPD) and may be of interest in non-eosinophilic asthma (NEA) which is also characterised by impaired efferocytosis. It was hypothesised that the addition of exogenous galectin-3 to monocyte-derived macrophages (MDMs) derived from donors with NEA would enhance their ability to engulf apoptotic granulocytes. METHODS:Eligible non-smoking adults with asthma (n?=?19), including 7 with NEA and healthy controls (n?=?10) underwent a clinical assessment, venepuncture and sputum induction. MDMs were co-cultured with apoptotic granulocytes isolated from healthy donors with or without exogenous recombinant galectin-3 (50??g/mL) and efferocytosis was assessed by flow cytometry. Galectin-3 expression and localisation in MDMs was visualised by immunofluorescence staining and fluorescence microscopy. Galectin-3, interleukin (IL)-6 and CXCL8 secretion were measured in cell culture supernatants by ELISA and cytometric bead array. RESULTS:Baseline efferocytosis (mean (±standard deviation)) was lower in participants with asthma (33.2 (±17.7)%) compared with healthy controls (45.3 (±15.9)%; p?=?0.081). Efferocytosis did not differ between the participants with eosinophilic asthma (EA) (31.4 (±19.2)%) and NEA (28.7 (±21.5)%; p?=?0.748). Addition of galectin-3 significantly improved efferocytosis in asthma, particularly in NEA (37.8 (±18.1)%) compared with baseline (30.4 (±19.7)%; p?=?0.012). Efferocytosis was not associated with any of the clinical outcomes but was negatively correlated with sputum macrophage numbers (Spearman r?=?-?0.671; p?=?0.017). Galectin-3 was diffusely distributed in most MDMs but formed punctate structures in 5% of MDMs. MDM galectin-3 secretion was lower in asthma (9.99 (2.67, 15.48) ng/mL) compared with the healthy controls (20.72 (11.28, 27.89) ng/mL; p?=?0.044) while IL-6 and CXCL8 levels were similar. CONCLUSIONS:Galectin-3 modulates macrophage function in asthma, indicating a potential role for galectin-3 to reverse impaired efferocytosis in NEA.
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Project description:To investigate the chemokines expressed by the KP cancer line and to compare it to chemokines expressed in lung tissues upon inoculation of KP tumor cells
2022-04-07 | GSE200126 | GEO
Project description:CD8 T cell responses against different tumor neoantigens occur simultaneously, yet little is known about the interplay of these responses or its impact on tumor control. Here, we characterized the CD8 T cell response against two co-expressed tumor neoantigens, SIINFEKL (SIIN) and SIYRYYGL (SIY), in a genetically engineered mouse model of lung adenocarcinoma. In this model, tumors are initiated in KrasLSLG12D;p53fl/fl (KP) mice by intratracheal installation of lentiviruses expressing Cre recombinase and the antigens as a fusion to luciferase (LucOS). In these KP LucOS mice, the CD8 T cell response peaks around 5 weeks post-tumor initiation and is dominated by expansion of cells specific to SIIN. SIY drives a much smaller T cell response, but it persists better over time. To further investigate phenotypic differences in the T cell responses against SIIN versus SIY, we subjected antigen-specific CD8 T cells from 5 week mice to paired single cell RNA and TCR sequencing using the 10X Genomics platform.
2021-09-16 | GSE164177 | GEO