RGD Reference Report - Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4. - Rat Genome Database

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Human Immunodeficiency Virus Type-1 Myeloid Derived Suppressor Cells Inhibit Cytomegalovirus Inflammation through Interleukin-27 and B7-H4.

Authors: Garg, Ankita  Trout, Rodney  Spector, Stephen A 
Citation: Garg A, etal., Sci Rep. 2017 Mar 24;7:44485. doi: 10.1038/srep44485.
RGD ID: 126790518
Pubmed: PMID:28338007   (View Abstract at PubMed)
PMCID: PMC5364511   (View Article at PubMed Central)
DOI: DOI:10.1038/srep44485   (Journal Full-text)

HIV/CMV co-infected persons despite prolonged viral suppression often experience persistent immune activation, have an increased frequency of myeloid derived suppressor cells (MDSC) and are at increased risk for cardiovascular disease. We examined how HIV MDSC control CD4+ T cell IFNγ response to a CMVpp65 peptide pool (CMVpp65). We show that HIV/CMV co-infected persons with virologic suppression and recovered CD4+ T cells compared to HIV(-)/CMV(+) controls exhibit an increase in CD4+CX3CR1+IFNγ+ cells in response to CMVpp65; MDSC depletion further augmented CD4+CX3CR1+IFNγ+ cells and IFNγ production. IL-2 and IFNγ in response to CMVpp65 were enhanced with depletion of MDSC expanded in presence of HIV (HIV MDSC), but decreased with culture of HIV MDSC with autologous PBMCs. CMVpp65 specific CD4+CX3CR1+IFNγ+ cells were also decreased in presence of HIV MDSC. HIV MDSC overexpressed B7-H4 and silencing B7-H4 increased the production of IL-2 and IFNγ from autologous cells; a process mediated through increased phosphorylated (p)-Akt upon stimulation with CMVpp65. Additionally, IL-27 regulated the expression of B7-H4 on HIV MDSC, and controlled CMV-specific T cell activity by limiting CMVpp65-IFNγ production and expanding CD4+IL-10+ regulatory T cells. These findings provide new therapeutic targets to control the chronic immune activation and endothelial cell inflammation observed in HIV-infected persons.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL27Humanhuman immunodeficiency virus infectious disease amelioratesIEP protein:increased expression:blood plasma (human)RGD 
Il27Rathuman immunodeficiency virus infectious disease amelioratesISOIL27 (Homo sapiens)protein:increased expression:blood plasma (human)RGD 
Il27Mousehuman immunodeficiency virus infectious disease amelioratesISOIL27 (Homo sapiens)protein:increased expression:blood plasma (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Il27  (interleukin 27)

Genes (Mus musculus)
Il27  (interleukin 27)

Genes (Homo sapiens)
IL27  (interleukin 27)


Additional Information