Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human monocyte subpopulations

ABSTRACT: In vivo studies in mice have identified subsets of monocytes involved in the inflammatory response to pathogens, but their respective functions remains poorly understood. We report that human CD14+ monocytes represent functional ortholog to mouse Ly6C+ monocytes and are responsible for phagocytosis, Reactive Oxygen Species (ROS) and cytokine production in response to a broad range of pathogen associated molecular patterns (PAMP). In contrast a discrete population of CD14dim cells are ortholog to the mouse ly6C- monocytes and share their ability to patrol the endothelium of blood vessels, but do not produce ROS, are weak phagocytes, and poorly respond to bacterial PAMPs. Instead, CD14dim monocytes are critical for production of pro-apoptotic and pro-inflammatory cytokines in response to viruses and nucleic acids via a unique TLR7-8/MyD88/MEK pathway, while they may also contribute to tissue damage in autoimmune diseases such as Lupus.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicolas Cagnard

PROVIDER: E-MEXP-2544 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:BACKGROUND: Combination antiretroviral therapy (cART) is able to control HIV-1 viral replication, however long-lived latent infection in resting memory CD4+ T-cells persist. The mechanisms for establishment and maintenance of latent infection in resting memory CD4+ T-cells remain unclear. Previously we have shown that HIV-1 infection of resting CD4+ T-cells co-cultured with CD11c+ myeloid dendritic cells (mDC) produced a population of non-proliferating T-cells with latent infection. Here we asked whether different antigen presenting cells (APC), including subpopulations of DC and monocytes, were able to induce post-integration latent infection in resting CD4+ T-cells, and examined potential cell interactions that may be involved using RNA-seq. RESULTS: mDC (CD1c+), SLAN+ DC and CD14+ monocytes were most efficient in stimulating proliferation of CD4+ T-cells during syngeneic culture and in generating post-integration latent infection in non-proliferating CD4+ T-cells following HIV-1 infection of APC-T-cell co-cultures. In comparison, plasmacytoid DC (pDC) and B-cells did not induce latent infection in APC-T-cell co-cultures. We compared the RNA expression profiles of APC subpopulations that could and could not induce latency in non-proliferating CD4+ T-cells. Gene expression analysis, comparing the mDC, SLAN+ DC and CD14+ monocyte subpopulations to pDC identified 53 upregulated genes that encode proteins expressed on the plasma membrane that could signal to CD4+ T-cells via cell-cell interactions (32 genes), immune checkpoints (IC) (5 genes), T-cell activation (9 genes), regulation of apoptosis (5 genes), antigen presentation (1 gene) and through unknown ligands (1 gene). CONCLUSIONS: APC subpopulations from the myeloid lineage, specifically mDC subpopulations and CD14+ monocytes, were able to efficiently induce post-integration HIV-1 latency in non-proliferating CD4+ T-cells in vitro. Inhibition of key pathways involved in mDC-T-cell interactions and HIV-1 latency may provide novel targets to eliminate HIV latency. mRNA profiles of sorted, pure antigen presenting cells including, CD1c+ myleoid dendirtic cells (mDC), SLAN+ mDC, CD14+ monocytes and plasmacytoid DC (pDC), were generated using next generation sequencing in triplicate, using Illumina Illumina Hiseq 2000.

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Transcription profiling of human monocyte subpopulations

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