Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16
            <sup>+</sup>
            Monocytes

Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M.; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N’Faly; Gabriel, Marcin; Günther, Stephan; Oestereich, Lisa; Muñoz‐Fontela, César

doi:10.1093/infdis/jiw260

Cited by 30 publications

(28 citation statements)

References 15 publications

(19 reference statements)

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“…Consistent with these observations, the ability of EBOV to infect and replicate in Mϕs and DCs has also been confirmed in numerous tissue culture models . Surprisingly, the role of circulating monocytes during filovirus infection is poorly studied and only recently examined . However, these studies suggest that this mononuclear phagocytic population may also play an important role during infection.…”

Section: Mononuclear Phagocytes: Origins and Functionsmentioning

confidence: 60%

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The role of mononuclear phagocytes in Ebola virus infection

Rogers

Maury

2018

Journal of Leukocyte Biology

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The filovirus, Zaire Ebolavirus (EBOV), infects tissue macrophages (Mϕs) and dendritic cells (DCs) early during infection. Viral infection of both cells types is highly productive, leading to increased viral load. However, virus infection of these two cell types results in different consequences for cellular function. Infection of Mϕs stimulates the production of proinflammatory and immunomodulatory cytokines and chemokines, leading to the production of a cytokine storm, while simultaneously increasing tissue factor production and thus facilitating disseminated intravascular coagulation. In contrast, EBOV infection of DCs blocks DC maturation and antigen presentation rendering these cells unable to communicate with adaptive immune response elements. Details of the known interactions of these cells with EBOV are reviewed here. We also identify a number of unanswered questions that remain about interactions of filoviruses with these cells.

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Section: Mononuclear Phagocytes: Origins and Functionsmentioning

confidence: 60%

“…Other studies support a role for circulating PBMCs in active EBOV infection . A recent longitudinal study in a patient with severe EVD demonstrated that virus load in PBMCs correlates well with serum RNA levels, suggesting that virus replication in PBMCs contributes significantly to overall virus load.…”

Section: The Role Of Monocytes During Filovirus Infectionmentioning

confidence: 92%

The role of mononuclear phagocytes in Ebola virus infection

Rogers

Maury

2018

Journal of Leukocyte Biology

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“…Thus, an analysis of the vaccine-modulated expression of genes that correlated with a risk of SIV mac251 acquisition strongly supported the opposite roles of the different monocyte subsets, with the activation of hypoxia and inflammasome pathways in CD14 + monocytes associated with a decreased risk of SIV mac251 acquisition, and the activation STAT3 in CD16 + monocytes with an increased risk of acquisition. Monocyte subsets also display discordant roles in immunity against other infectious viruses, including Zika virus, Ebola virus, Dengue virus, Epstein–Barr virus and SIV/HIV 26,27 . We next investigated monocyte-mediated phagocytosis in the presence or absence of anti-SIV antibodies.…”

Section: Resultsmentioning

confidence: 99%

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Vaccari

Fourati

Gordon

et al. 2018

Nat Med

108

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Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)–SIV, DNA–SIV and Ad26–SIV vaccine prime modalities together with two ALVAC–SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+CD16− monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition. By contrast, signal transducer and activator of transcription 3 activation in CD16+ monocytes was associated with an increased risk of virus acquisition. The Ad26 prime regimen induced the accumulation of CX3CR1+CD163+ macrophages in lymph nodes and of long-lasting CD4+ TH17 cells in the gut and lungs. Our data indicate that the selective engagement of monocyte subsets following a vaccine prime influences long-term immunity, uncovering an unexpected association of CD14+ innate monocytes with a reduced risk of SIVmac251 acquisition.

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“…Nonetheless, our network analysis approach separated PBMC transcriptomics data into modules of co-expressed transcripts that included well-established markers of different immune cell types, which enabled us to infer immune cell population-specific contributions to EVD pathogenicity. Additional studies will be required to precisely gauge the impact of EVD-driven changes in peripheral immune cell populations on PBMC transcript expression, particularly for neutrophils, which are markedly increased in the periphery of some EVD patients (Hunt et al, 2015) but probably accumulate at similar levels in survivors and fatalities (Ludtke et al, 2016). …”

Section: Discussionmentioning

confidence: 99%

“…In contrast, T lymphocytes in fatal infections exhibit pronounced immunosuppressive marker (PD-1/PDCD1 and CTLA4) expression and low EBOV protein specificity (Ruibal et al, 2016). The role of antigen presenting cells (APCs) is not fully understood, but a recent report suggested that monocytes may be inefficiently activated (Ludtke et al, 2016). Notably, systemic inflammation and immune dysfunction, as well as other clinical EVD findings (i.e., coagulopathies, vascular leakage, and organ dysfunction), are characteristic of classical sepsis caused by other disease agents (Hellman, 2015).…”

Section: Introductionmentioning

confidence: 99%

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

Eisfeld

Halfmann

Wendler

et al. 2017

Cell Host & Microbe

113

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SUMMARY The pathogenesis of Human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ‘omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that EBOV infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

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Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16 ⁺ Monocytes

Cited by 30 publications

References 15 publications

The role of mononuclear phagocytes in Ebola virus infection

The role of mononuclear phagocytes in Ebola virus infection

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

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Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16 + Monocytes

Cited by 30 publications

References 15 publications

The role of mononuclear phagocytes in Ebola virus infection

The role of mononuclear phagocytes in Ebola virus infection

HIV vaccine candidate activation of hypoxia and the inflammasome in CD14+ monocytes is associated with a decreased risk of SIVmac251 acquisition

Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

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Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16 ⁺ Monocytes