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Human cytomegalovirus reprograms hematopoietic progenitor cells into immunosuppressive monocyte to achieve latency

ABSTRACT: HCMV NR-1 infection reprograms human CD34+ HPCs into long-life, NO-producing, immune suppressive Mo-MDSC-like cells at the late stage of infection We used microarray to detail the gene expression of human CD34+ HPCs and long-life, NO-producing, immune suppressive Mo-MDSC-like cells at the late stage of infection

ORGANISM(S): Homo sapiens

PROVIDER: GSE106879 | GEO | 2017/11/15

SECONDARY ACCESSION(S): PRJNA418309

REPOSITORIES: GEO

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Comparative quantitative proteomic analysis of HCMV infected cells highlights pUL138 as a multiple functional protein

Project description:Human cytomegalovirus (HCMV) is a widespread virus and can establish life-long latent infection in large populations. In order to establish persistent and latent infection in healthy individuals, HCMV encodes a large array of proteins that can modulate different components and pathways of host cells. It has been reported that pUL138 encoded by UL133-UL138 polycistronic locus promotes a latent infection in primary CD34+ HPCs infected in vitro. In this study, a recombinant HCMV, namely HanUL138del, was constructed by deleting the UL138 locus of Han, a clinic HCMV strain. Then a comparative quantitative proteomic analysis of Han and HanUL138del infected MRC5 cells was performed, aiming to study the effect of pUL138 on host cell in the context of HCMV infection. Our result indicated that at the early phase of HCMV infection, innate immune response was differentially activated, while at late phase of HCMV infection, multiple host proteins were differentially expressed, between Han or HanUL138del infected cells.

2021-09-08 | PXD015931 | Pride

Monocytic myeloid-derived suppressor cells accumulate in the lungs of influenza A virus-infected mice

Project description:Influenza A virus (IAV) infection causes an acute respiratory disease characterized by a strong inflammatory immune response and severe immunopathology. Pro-inflammatory mechanisms are well described in the murine IAV infection model, but less is known about the mechanisms leading to the resolution of inflammation. Here, we analyzed the contribution of monocytic myeloid-derived suppressor cells (mono-MDSC) to this process. An accumulation of mono-MDSC within the lungs was observed during the course of IAV infection and phenotypic characterization of these mono-MDSC by flow cytometry and RNA-Seq revealed an activated phenotype showing both pro- and anti-inflammatory features, including the expression of iNOS by a fraction of cells in an IFN-g-dependent manner. Mono-MDSC isolated from lungs of IAV-infected animals displayed suppressive activity when tested in vitro, and iNOS inhibitors could abrogate this suppressive activity. Collectively, our data suggest that during IAV infection monocytes can differentiate into mono-MDSC, which might contribute to the prevention of immunopathology during this life-threatening disease.

2015-10-01 | GSE62795 | GEO

Healthy Myeloid-Derived Suppressor Cells Express the Surface Ectoenzyme Vanin-2 (VNN2)

Project description:Study of human monocytic Myeloid-Derived Suppressor cells Mo-MDSC (CD14+ HLA-DRneg/low) has been hampered by the lack of positive cell-surface markers. In order to identify positive markers for Mo-MDSC, we performed microarray analysis comparing Mo-MDSC cells from healthy subjects versus CD14+ HLA-DRhigh monocytes. We have identified the surface ectoenzyme Vanin-2(VNN2) protein as a novel biomarker highly-enriched in healthy subjects Mo-MDSC. Indeed, healthy subjects Mo-MDSC cells expressed 68% VNN2, whereas only 9% VNN2 expression was observed on CD14+ HLA-DRhigh cells (n=4 p<0.01). The top 10 percent positive VNN2 monocytes expressed CD33 and CD11b while being negative for HLA-DR, CD3, CD15, CD19 and CD56, consistent with a Mo-MDSC phenotype. CD14+VNN2high monocytes were able to inhibit CD8 T cell proliferation comparably to traditional Mo-MDSC at 51% and 48% respectively. However, VNN2 expression on CD14+ monocytes from glioma patients was inversely correlated to their grade. CD14+VNN2high monocytes thus appear to mark a monocytic population similar to Mo-MDSC only in healthy subjects, which may be useful for tumor diagnoses. Myeloid-Derived Suppressor Cells (MDSC) are identified by upregulated expression of the cell surface ectoenzyme Vanin-2 in healthy subjects

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Expression data from granulocytic MDSC (G-MDSC) and neutrophils

Project description:Myeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions what’s the difference between G-MDSC and neutrophils but it’s not yet proven clearly. In this study, we examined the gene expression of G-MDSC and neutrophils using Affymetrix microarray G-MDSC (CD11b+Ly6G+Ly6Clow) were purifed from splenocytes in EL4 lymphoma tumor bearing mice by positive selection of Ly6G using microbeads isolation. Neutrophils were purified from ascitic fluids induced after injection of milk protein, casein by negative selection of F4/80 and positive selection of Ly6G using microbeads isolation. Their RNA was extracted and gene expression was analyzed using Affymetrix microarray.

2011-03-10 | E-GEOD-24102 | biostudies-arrayexpress

Expression data from granulocytic MDSC (G-MDSC) and neutrophils

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Expression data from human CD34+ HPC subpopulations isolated from umbilical cord blood (Haddad et al. Blood 104:3918, 2004)

Project description:We used microarrays to analyze the gene expression profile of CD34+CD45RA+CD7+, CD34+CD45RA+CD10+CD19- and CD34+CD45+CD7-CD10-CD19- HPCs isolated from umbilical cord blood CD34+CD45RA+CD7+(CD10-) and CD34+CD45RA+CD10+(CD7-CD19-) HPCs correspond respectively to prothymocytes and early pre-proB precursors. CD34+CD45RA+CD7-CD10-CD19- HPCs correspond to lympho-granulo-macrophagic precursors

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Mechanisms regulating transitory suppressive activity of neutrophils in newborns

Project description:Transitory appearance of immune suppressive polymorphonuclear neutrophils (PMN) defined as myeloid-derived suppressor cells (PMN-MDSC) in newborns is important for their protection from inflammation associated with newly established gut microbiota. Here, we report that inhibition of the type I interferon (IFN1) pathway played a major role in regulation of PMN-MDSC suppressive activity during first weeks of life. Expression of the IFN1 receptor IFNAR1 was markedly lower in PMN-MDSC. However, in newborn mice, down-regulation of IFNAR1 was not sufficient to render PMN immune suppressive. That also required the presence of a positive signal from lactoferrin via its receptor LRP2. The latter effect was mediated via NF-kB activation, which was tempered by IFN1 in a manner that involved SOCS3. Thus, we discovered a mechanism of tight regulation of immune suppressive PMN-MDSC in newborns, which may be used in the development of therapies of neonatal pathologies

2022-05-31 | GSE202264 | GEO

Expression data from human CD34+ HPC subpopulations isolated from umbilical cord blood (Haddad et al. Blood 104:3918, 2004)

2011-05-25 | E-GEOD-29522 | biostudies-arrayexpress

Transitory accumulation of myeloid-derived suppressor cells in neonates is critical for maintenance of homeostasis

Project description:Myeloid-derived suppressor cells (MDSC) are potent negative regulators of immune responses at many pathological conditions. It is widely accepted that these cells are not present under steady state condition. Here, we report that MDSC with highly potent ability to suppress T cells accumulate during first two weeks of life in mice. MDSC suppressive activity in neonates was triggered by lactoferrin, a component of milk, and mediated by nitric oxide and up-regulation of PGE2 regulated by S100A9/A8 proteins. Newborn MDSC had transcriptome similar to that of tumor MDSC. However, they had strong up-regulation of antimicrobial gene network. This was associated with enhanced antimicrobial activity of these cells. MDSC played a critical role in control of experimental necrotizing enterocolitis in newborn mice. In humans, MDSC in cord blood of low-weight preterm infants prone to the development of NEC had significantly lower suppressive activity than the cells from cord blood of infants with normal weight. Thus, transitory presence of MDSC after birth is critical for the maintenance of immune homeostasis.

2018-01-03 | GSE97993 | GEO

Expression data from human CD34+ HPC subpopulations transduced with nuclear-trapped AF1q/MLLT11 (A2M)

Project description:We used microarrays to examine the impact of AF1q/MLLT11 on the gene expression profile of CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs isolated from umbilical cord blood CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs correspond respectively to early multipotent and lympho-granulo-macrophagic precursors. A2M is a nuclear mutant-derivative of AF1q/MLLT11 CD34+CD45RA-Lin- and CD34+CD45RA+Lin- HPCs were FACS-sorted, exposed to A2M or control vectors, sorted based on GFP expression, and subjected to global gene expression analysis 72 hrs later.

2011-05-26 | E-GEOD-29523 | biostudies-arrayexpress

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