Dataset Information

Human monocyte-derived macrophages inhibit HCMV spread independent of classical antiviral cytokines.

ABSTRACT: Infection of healthy individuals with human cytomegalovirus (HCMV) is usually unnoticed and results in life-long latency, whereas HCMV reactivation as well as infection of newborns or immunocompromised patients can cause life-threatening disease. To better understand HCMV pathogenesis we studied mechanisms that restrict HCMV spread. We discovered that HCMV-infected cells can directly trigger plasmacytoid dendritic cells (pDC) to mount antiviral type I interferon (IFN-I) responses, even in the absence of cell-free virus. In contrast, monocyte-derived cells only expressed IFN-I when stimulated by cell-free HCMV, or upon encounter of HCMV-infected cells that already produced cell-free virus. Nevertheless, also in the absence of cell-free virus, i.e., upon co-culture of infected epithelial/endothelial cells and monocyte-derived macrophages (moM?) or dendritic cells (moDC), antiviral responses were induced that limited HCMV spread. The induction of this antiviral effect was dependent on cell-cell contact, whereas cell-free supernatants from co-culture experiments also inhibited virus spread, implying that soluble factors were critically needed. Interestingly, the antiviral effect was independent of IFN-?, TNF-?, and IFN-I as indicated by cytokine inhibition experiments using neutralizing antibodies or the vaccinia virus-derived soluble IFN-I binding protein B18R, which traps human IFN-? and IFN-?. In conclusion, our results indicate that human macrophages and dendritic cells can limit HCMV spread by IFN-I dependent as well as independent mechanisms, whereas the latter ones might be particularly relevant for the restriction of HCMV transmission via cell-to-cell spread.

SUBMITTER: Becker J

PROVIDER: S-EPMC7000197 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Human monocyte-derived macrophages inhibit HCMV spread independent of classical antiviral cytokines.

Becker Jennifer J Kinast Volker V Döring Marius M Lipps Christoph C Duran Veronica V Spanier Julia J Tegtmeyer Pia-Katharina PK Wirth Dagmar D Cicin-Sain Luka L Alcamí Antonio A Kalinke Ulrich U

Virulence 20180101 1

Infection of healthy individuals with human cytomegalovirus (HCMV) is usually unnoticed and results in life-long latency, whereas HCMV reactivation as well as infection of newborns or immunocompromised patients can cause life-threatening disease. To better understand HCMV pathogenesis we studied mechanisms that restrict HCMV spread. We discovered that HCMV-infected cells can directly trigger plasmacytoid dendritic cells (pDC) to mount antiviral type I interferon (IFN-I) responses, even in the ab ...[more]

PMID: 30403913

Similar Datasets

Project description:BackgroundMesenchymal stem/stromal cells (MSCs) and macrophages are critical components in many tissue microenvironments, including that in adipose tissue. The close interaction between MSCs and macrophages modulates various adipose-related disease development. However, the effects of macrophages on the fate of MSCs remain largely elusive. We here studied the effect of macrophages on the adipogenic differentiation of MSCs.MethodsMacrophages were obtained from THP-1 cells treated with phorbol-12-myristate-13-acetate (PMA). The induced matured macrophages were then induced to undergo classically activated macrophage (M1) or alternatively activated macrophage (M2) polarization with Iipopolysaccharide (LPS)/interferon (IFN)-γ and interleukin (IL)-4/IL-13, respectively. The supernatants derived from macrophages under different conditions were applied to cultured human adipose tissue-derived mesenchymal stem/stromal cells (hADSCs) undergoing adipogenic differentiation. Adipogenic differentiation was evaluated by examining Oil Red O staining of lipid droplets and the expression of adipogenesis-related genes with real-time quantitative polymerase chain reaction (Q-PCR) and western blot analysis.ResultsThe adipogenic differentiation of hADSCs was impaired when treated with macrophage-derived supernatants, especially that from the M1-polarized macrophage (M1-sup). The inhibitory effect was found to be mediated by the inflammatory cytokines, mainly tumor necrosis factor-α (TNF-α) and IL-1β. Blocking TNF-α and IL-1β with neutralizing antibodies partially alleviated the inhibitory effect of M1-sup.ConclusionMacrophage-derived supernatants inhibited the adipogenic differentiation of hADSCs in vitro, irrespective of the polarization status (M0, M1 or M2 macrophages). M1-sup was more potent because of the higher expression of pro-inflammatory cytokines. Our findings shed new light on the interaction between hADSCs and macrophages and have implications in our understanding of disrupted adipose tissue homeostasis under inflammation.

Project description:Human cytomegalovirus (HCMV) is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs). This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages. Consequently, it has been suggested that macrophages and dendritic cells contribute to viral spread in vivo. Thus far only limited knowledge is available on the expression of HCMV genes in terminally differentiated myeloid primary cells and whether or not the virus exhibits a different set of lytic genes in primary cells compared with lytic infection in NHDF fibroblasts. To address these questions, we used Illumina next generation sequencing to determine the HCMV transcriptome in macrophages and dendritic cells during lytic infection and compared it to the transcriptome in NHDF fibroblasts. Here, we demonstrate unique expression profiles in macrophages and dendritic cells which significantly differ from the transcriptome in fibroblasts mainly by modulating the expression of viral transcripts involved in immune modulation, cell tropism and viral spread. In a head to head comparison between macrophages and dendritic cells, we observed that factors involved in viral spread and virion composition are differentially regulated suggesting that the plasticity of the virion facilitates the infection of surrounding cells. Taken together, this study provides the full transcript expression analysis of lytic HCMV genes in monocyte-derived type 1 and type 2 macrophages as well as in monocyte-derived dendritic cells. Thereby underlining the potential of HCMV to adapt to or influence different cellular environments to promote its own survival.

Dataset Information

Human monocyte-derived macrophages inhibit HCMV spread independent of classical antiviral cytokines.

Publications

Human monocyte-derived macrophages inhibit HCMV spread independent of classical antiviral cytokines.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets