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The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

ABSTRACT: Splenic dendritic cells were isolated and processed using 10X genomics 3' gene expression kit v3.1, to assess APOL7C expression and response to poly(I:C)

ORGANISM(S): Mus musculus

PROVIDER: GSE278170 | GEO | 2024/09/27

REPOSITORIES: GEO

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The pore-forming apolipoprotein APOL7C drives phagosomal rupture and antigen cross-presentation by dendritic cells

Project description:Conventional dendritic cells (cDCs) generate protective cytotoxic T lymphocyte (CTL) responses against pathogens and tumours. This is achieved through a process known as cross-presentation (XP) and, despite its obvious biological importance, the mechanism(s) driving XP remain unclear. Here, we show that a cDC-specific pore-forming protein called apolipoprotein L 7C (APOL7C) is upregulated in response to innate immune stimuli and is recruited to phagosomes. Strikingly, its association with phagosomes leads to phagosomal rupture. This allows for the escape of engulfed antigens to the cytosol where they can be processed via the endogenous MHC class I antigen processing pathway. Accordingly, mice deficient in APOL7C do not efficiently prime CD8+ T cells in response to immunization with bead-bound and cell-associated antigens. Altogether, our data indicate the presence of dedicated apolipoproteins that mediate the delivery of phagocytosed proteins to the cytosol of activated cDCs to facilitate XP.

2024-09-25 | GSE276376 | GEO

The Vacuolar Pathway in Macrophages Plays a Major Role in Antigen Cross-Presentation Induced by the Pore-Forming Protein Sticholysin II Encapsulated Into Liposomes.

Project description:Cross-presentation is an important mechanism for the differentiation of effector cytotoxic T lymphocytes (CTL) from naïve CD8+ T-cells, a key response for the clearance of intracellular pathogens and tumors. The liposomal co-encapsulation of the pore-forming protein sticholysin II (StII) with ovalbumin (OVA) (Lp/OVA/StII) induces a powerful OVA-specific CTL activation and an anti-tumor response in vivo. However, the pathway through which the StII contained in this preparation is able to induce antigen cross-presentation and the type of professional antigen presenting cells (APCs) involved have not been elucidated. Here, the ability of mouse bone marrow-derived dendritic cells (BM-DCs) and macrophages (BM-M?s) stimulated with Lp/OVA/StII to activate SIINFEKL-specific B3Z CD8+ T cells was evaluated in the presence of selected inhibitors. BM-M?s, but not BM-DCs were able to induce SIINFEKL-specific B3Z CD8+ T cell activation upon stimulation with Lp/OVA/StII. The cross-presentation of OVA was markedly decreased by the lysosome protease inhibitors, leupeptin and cathepsin general inhibitor, while it was unaffected by the proteasome inhibitor epoxomicin. This process was also significantly reduced by phagocytosis and Golgi apparatus function inhibitors, cytochalasin D and brefeldin A, respectively. These results are consistent with the concept that BM-M?s internalize these liposomes through a phagocytic mechanism resulting in the cross-presentation of the encapsulated OVA by the vacuolar pathway. The contribution of macrophages to the CTL response induced by Lp/OVA/StII in vivo was determined by depleting macrophages with clodronate-containing liposomes. CTL induction was almost completely abrogated in mice depleted of macrophages, demonstrating the relevance of these APCs in the antigen cross-presentation induced by this formulation.

| S-EPMC6230584 | biostudies-literature

Increased antigen cross-presentation but impaired cross-priming after activation of PPARÎ³

Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARÎ³ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor Î³ (PPARÎ³), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARÎ³ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARÎ³ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARÎ³ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity. Comparison of murine mannose receptor negative versus mannose receptor positive bone marrow-derived DCs

2010-05-08 | E-GEOD-15616 | biostudies-arrayexpress

Single-cell RNA sequencing (10x Genomics) of human peripheral blood mononuclear cells

Project description:Human PBMC cells were processed and prepared for sequencing using 10x Genomics Gene Expression 3' workflow v3.1

2022-05-16 | E-MTAB-11488 | biostudies-arrayexpress

Human distal lung maps and lineage hierarchies reveal a bipotent progenitor [human lung organoids]

Project description:We performed single-cell RNA-seq using 10x Genomic Chromium v3.1 on human lung organoid cultures.

2022-01-16 | GSE178519 | GEO

Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ

Project description:Increased antigen cross-presentation but impaired cross-priming after activation of PPARγ is mediated by up-regulation of B7H1 Dendritic cells (DCs) are able to take up exogenous antigens and present antigen-derived peptides on MHC class I molecules, a process termed cross-presentation. The mannose receptor (MR), an endocytic receptor expressed on a variety of antigen-presenting cells (APCs), has been demonstrated to target soluble antigens exclusively towards cross-presentation. In this study, we investigated the role of the murine nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ), a ligand-activated transcription factor with immunomodulatory properties, in MR-mediated endocytosis and cross-presentation of the model antigen ovalbumin (OVA). We could demonstrate both in vitro and in vivo that activation of PPARγ resulted in increased MR expression, which in consequence led to enhanced MR-mediated endocytosis and elevated cross-presentation of soluble OVA. Concomitantly, activation of PPARγ in DCs induced up-regulation of the co-inhibitory molecule B7H1, which, despite enhanced cross-presentation, caused an impaired activation of naive OVA-specific CD8+ T cells and the induction of T cell tolerance. These data provide a mechanistic basis for the immunomodulatory action of PPARγ which might open new possibilities in development of therapeutical approaches aimed at the control of excessive immune responses, e.g. in T cell-mediated autoimmunity.

2009-06-19 | GSE15616 | GEO

Human distal lung maps and lineage hierarchies reveal a bipotent progenitor [single-cell RNA-seq]

Project description:We performed single-cell RNA-seq using 10x Genomic Chromium v3.1 on micro-dissected human distal airways.

2022-01-16 | GSE178360 | GEO

Single-cell RNA-seq in AT2 cell-ablated mouse lungs

Project description:We performed single-cell RNA-seq using the chemistry of 10x Genomic Chromium v3.1 in mouse lungs following AT2 cell ablation.

2022-09-14 | GSE173878 | GEO

ACME dissociation: a versatile cell fixation-dissociation method for single-cell transcriptomics

Project description:We performed single-cell transcriptome analysis (using 10x genomics 3' scRNA-seq v3.1 chemistry) in the sea anemone Nematostella vectensis (Cnidaria).

2021-04-01 | GSE166977 | GEO

Influence of T and B lymphocytes on the antigen presentation capacities of splenic conventional dendritic cells

Project description:The goal of this project was to characterize DCs from lymphopenic mice, like RAG (recombination activated gene) deficient mice and to examine the influence of mature B and T cells on the antigen presenting ability of splenic cDCs. We demonstrate how cellular cross-talk can shape the character and function of cDCs. Lymphopenic conditions, where splenic cDCs have to develop and differentiate, drastically change their character and their ability to cross-present soluble antigen. In this approach we sorted out two populations (CD8?+ and CD8?-) of splenic dendritic cells (DCs) from untreated WT, and RAG2-/- C57Bl/6 mice. The age of mice was between 8-10 weeks. Further we isolated RNA and performed microarray analysis. Each DCs population was repeated twice.

2013-01-22 | E-GEOD-17989 | biostudies-arrayexpress

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