RNA seq analysis of human monocyte subsets in healthy and dengue subjects
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE176079 | GEO | 2022/05/16
REPOSITORIES: GEO
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Project description:Monocytes are short-lived myeloid immune cells that arise from adult hematopoiesis and circulate for a short time in the blood. They comprise two main subsets, in mice defined as classical Ly6Chigh and non-classical Ly6Clow monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM in the BM and blood. Functional characterization, including fate definition following adoptive cell transfer, established that GMP-Mo and MDP-Mo could equal rise to homeostatic CM progeny, such as NCM in blood and gut macrophages, but differentially seeded selected other tissues. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, thus linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide comprehensive evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge. Our findings are indicative of impact of monocyte ontogeny on in situ differentiation.
2024-05-04 | GSE261594 | GEO
Project description:Monocytes are ephemeral myeloid immune cells that arise from adult hematopoiesis and circulate in the blood. They comprise two main subsets, in mice defined as classical and non-classical monocytes (CM, NCM). Recent fate mapping and transcriptomic analyses revealed that CM themselves are heterogeneous. Here, we report surface markers that allow segregation of murine GMP- and MDP-derived CM, as well as their functional characterization, including fate definition following adoptive cell transfer. GMP-Mo and MDP- Mo gave equal rise to homeostatic CM progeny, such as blood NCM and gut macrophages; the cells however differentially seeded selected other tissues, including the dura mater and lung. Specifically, GMP-Mo and MDP-Mo gave rise to distinct interstitial lung macrophages, linking CM dichotomy to previously reported pulmonary macrophage heterogeneity. Collectively, we provide evidence for the existence of two functionally distinct CM subsets in the mouse, which differentially contribute to peripheral tissue macrophage populations in homeostasis and following challenge.
2024-05-04 | GSE261003 | GEO
Project description:Primary Graft Dysfunction (PGD) is the predominant cause of early graft loss following lung transplantation. We recently demonstrated that donor pulmonary intravascular non-classical monocytes (NCM) initiate neutrophil recruitment. Simultaneously, host-origin classical monocytes (CM) are mobilized from the spleen and, upon entry into the allograft, permeabilize the vascular endothelium to allow neutrophil extravasation necessary for PGD. Here, we show that CCL2-CCR2 axis is necessary for CM recruitment. Surprisingly, although intravital imaging and multichannel flow cytometry revealed that pharmacological or genetic depletion of donor NCM abrogated CM recruitment, single-cell RNAseq identified donor alveolar macrophages (AM) as predominant CCL2 secretors. Unbiased transcriptomic analysis of human and murine tissues combined with murine knockouts and chimeras indicated that while IL1β was secreted by multiple cell lineages, donor NCM were responsible for the early activation of AM and CCL2 release. IL1β production by NCM was NLRP3 inflammasome-dependent and inhibited by donor treatment using a clinically approved sulphonylurea, Glyburide. Production of CCL2 in the donor AM occurred through IL1R-dependent activation of PKC and NFκB-pathway. Accordingly, we show that IL1β-dependent paracrine interaction between donor NCM and AM leads to recruitment of host AM necessary for PGD. Since depletion of donor NCM, IL1β or IL1R antagonism, and inflammasome inhibition, abrogated recruitment of CM as well as PGD and are feasible using FDA-approved compounds, our findings have potential for immediate clinical translation.
2024-02-01 | GSE166679 | GEO
Project description:Monocytes were isolated from healthy donors PBMC and sorted for classical and non-classical monocyte subsets. RNA-seq was performed on unstimulated monocytes.
2018-11-09 | E-MTAB-6712 | biostudies-arrayexpress
Project description:Pulmonary fibrosis (PF) is a progressive fibrotic disease with a poor prognosis and suboptimal therapeutic options. Macrophages have been implicated in PF; however, the roles of macrophage subsets, particularly interstitial macrophages (IM), remain unknown. To address this issue, we performed time-series single-cell RNA sequencing (scRNA-seq) analysis in silica-induced PF model mice and clarify the characteristics of IM. In addition, to elucidate the origin of IM, we used CCR2-/- mice which supressed classical monocyte infiltration.
2022-02-15 | GSE184854 | GEO
Project description:We measured fever-day-specific genome-wide transcript abundance patterns in 105 peripheral blood mononuclear cell (PBMC) samples collected from 41 children hospitalized with dengue virus (DENV) infection in Nicaragua, and from 8 healthy controls. DF1 = primary DF; DF2 = secondary DF; DHF = Dengue Hemorrhagic Fever; DSS = Dengue Shock Syndrome. Samples were collected from pediatric patients with DENV infection at the Hospital Infantil Manuel de Jesus Rivera (HIMJR) in Managua, Nicaragua. Enrollment criteria consisted of hospitalized patients younger than 15 years of age whose parents or guardians completed the informed consent process, and for children 6 years and older who provided assent, and who presented with acute febrile illness of less than 7 days duration with one or more of the following symptoms or signs at the time of evaluation: headache, arthralgia, myalgia, retro-orbital pain, positive tourniquet test, petechiae, and signs of bleeding. Children were considered to have dengue if DENV was detected by RT-PCR or by isolation in cell culture, if an IgM ELISA indicated seroconversion between the acute and convalescent sample, and/or if there was a > 4-fold increase in DENV-specific antibodies between the acute and convalescent phase. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood within four hours of collection and stored in Trizol at -80 oC disease_state_design
2013-03-01 | E-GEOD-38246 | biostudies-arrayexpress
Project description:- Here, we have isolated EVs from the plasma of three different groups Healthy donors (HD), Other febrile illness(OFI), and Severe dengue disease(SDV) by ultracentrifugation process. And proteomics of these EVs analyzed.
2023-10-25 | PXD045894 | Pride
Project description:Viral infections are among the most common causes for fever without an apparent source (FWS) in young children; however, many febrile children are treated with antibiotics despite the absence of bacterial infection. Adenovirus, human herpesvirus 6 (HHV-6) and enterovirus are detected in children with FWS more often than other viral species. Virus and bacteria interact with pattern recognition receptors in circulating blood leukocytes and trigger specific host transcriptional programs that mediate immune response, and unique transcriptional signatures may be ascertained to discriminate between viral and bacterial causes for children with FWS. Microarray analyses were conducted on peripheral blood samples obtained from 51 pediatric patients with confirmed adenovirus, human herpesvirus 6 (HHV-6), enterovirus or bacterial infection. Whole blood transcriptional profiles could clearly distinguish febrile children from healthy controls, and febrile children with viral infections from afebrile children carrying the same virus. Molecular pathways regulating host immune response were the most affected in febrile children with infection. Pattern recognition programs were prominently activated in all febrile children with infection, while differential activation of transcriptional programs was observed among viral species. Interferon signaling pathway was uniquely activated in children with febrile viral infection, while a different set of pathways was uniquely activated in children with bacterial infection. Transcriptional signatures were identified and classified febrile children with viral or bacterial infection with 87% overall accuracy, an improvement from the current clinical practice of deducing from white blood cell (WBC) count status. Similar degree of accuracy was observed when we validated the signature probes on data sets from an independent study with different microarray platforms. The current study confirms the clinical utility of blood transcriptional analysis, suggests the composition of transcriptional signatures which can be used to ascertain the infectious etiology of febrile young children without an apparent source, thus limit the overuse of antibiotics on febrile children presenting with this common clinical complaint. Total RNA samples extracted from whole blood of young children were processed for hybridization onto Illumina Human-HT12 version 4 beadchips, and differential expression of the transcripts was analyzed between sick children with either viral or bacterial infection and healthy children.
2012-10-15 | E-GEOD-40396 | biostudies-arrayexpress
Project description:Monocytes are a heterogeneous cell population with subset-specific functions and phenotypes. The differential expression of CD14 and CD16 distinguishes classical CD14++CD16-, intermediate CD14++CD16+ and non-classical CD14+CD16++ monocytes. However, CD14++CD16+ monocytes remain the most poorly characterized subset so far. Therefore we analyzed the transcriptomes of the three monocyte subsets using SuperSAGE in combination with high-throughput sequencing. Analysis of 5,487,603 tags revealed unique identifiers of CD14++CD16+ monocytes, delineating these cells from the two other monocyte subsets. CD14++CD16+ monocytes were linked to antigen processing and presentation (e.g. CD74, HLA-DR, IFI30, CTSB), to inflammation and monocyte activation (e.g. TGFB1, AIF1, PTPN6), and to angiogenesis (e.g. TIE2, CD105). Therefore we provide genetic evidence for a distinct role of CD14++CD16+ monocytes in human immunity. Human monocyte subsets (CD14++CD16-, CD14++CD16+, CD14+CD16++) were isolated from 12 healthy volunteers based on MACS technology. Total RNA from monocyte subsets was isolated and same aliquots from each donor and monocyte subset were matched for SuperSAGE. Three SuperSAGE libraries (CD14++CD16-, CD14++CD16+ and CD14+CD16++) were generated.
2011-07-24 | E-GEOD-30811 | biostudies-arrayexpress
Project description:Current non-specific immunosuppressive treatments for Systemic Lupus Erythematosus (SLE) show modest efficacy. In SLE the monocytic/macrophage (Mo/Mφ) system plays a key role in the initiation and perpetuation of the systemic autoimmune response. However, the distinct functions of the Mo/Mφ cellular subsets remain elusive. Herein, we demonstrate a distinct proteomic and transcriptomic profile of non-classical monocytes (NCM) of active patients with SLE with enhanced inflammatory features such as deregulated DNA repair, cell cycle and enhanced IFN signaling in parallel with cell differentiation and developmental cues. Ex-vivo assays revealed an upregulation of p53 due to enhanced DNA damage along with G0 cell cycle arrest of SLE NCM indicative of an inflammatory phenotype. This aberrant profile of NCM of active patients with SLE is linked with an activated macrophage-like and enriched M1 pro-inflammatory response. We envisage that enhanced autophagy in SLE NCM may drive their differentiation towards an M1-like macrophage profile contributing to disease severity. Together, these findings provide evidence of skewed differentiation of NCM towards an M1-like macrophage phenotype as a pathogenic feature of NCM in SLE.
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