LitCovid-sentences  

PMC:7200337 / 13173-21314 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T77 0-13 Sentence denotes Myeloid Cells
T78 14-283 Sentence denotes Mucosal immune responses to infectious agents are orchestrated and regulated by myeloid cells with specialized functions, which include conventional dendritic cells (cDCs), monocyte-derived DCs (moDCs), plasmacytoid DCs (pDCs), and macrophages (Guilliams et al., 2013).
T79 284-529 Sentence denotes A growing body of evidence points to dysregulated myeloid responses that potentially drive the COVID-19 hallmark syndromes, such as acute respiratory distress syndrome (ARDS), cytokine release syndrome (CRS) and lymphopenia (Mehta et al., 2020).
T80 531-567 Sentence denotes Myeloid Characterization in COVID-19
T81 568-927 Sentence denotes Flow cytometric analyses of peripheral blood mononuclear cells (PBMCs) from symptomatic COVID-19 patients have shown a significant influx of granulocyte-macrophage colony-stimulating factor (GM-CSF)-producing, activated CD4+ T cells and CD14+HLA-DRlo inflammatory monocytes (IMs) (Giamarellos-Bourboulis et al., 2020, Zhang et al., 2020c, Zhou et al., 2020b).
T82 928-1372 Sentence denotes This matches single-cell transcriptomic (scRNA-seq) data demonstrating CD14+IL-1β+ monocytic expansion (Guo et al., 2020, Wen et al., 2020), interferon-mitogen-activated protein kinase (MAPK)-driven adaptive immune responses (Huang et al., 2020c), and IL-1β-associated inflammasome signatures (Ong et al., 2020) in peripheral blood of COVID-19 patients, although systemic levels of IL-1β detected are conspicuously low (Del Valle et al., 2020).
T83 1373-1714 Sentence denotes Importantly, these immune signatures track with progression of clinical disease. scRNA-seq studies performed on pulmonary tissues of patients with severe COVID-19 disease have revealed an expansion of IMs and Ficolin-1+ monocyte-derived macrophages at the expense of tissue-resident reparative alveolar macrophages (AMs) (Liao et al., 2020).
T84 1715-1888 Sentence denotes The aforementioned study also observed signatures of IFN signaling and monocyte recruitment that likely contribute to the rapid decline in alveolar patency and promote ARDS.
T85 1889-2134 Sentence denotes Although most of the clinical focus has been on pulmonary damage and mononuclear phagocyte (MNP) dysfunction therein, it is increasingly clear that COVID-19 likely presents systemic challenges in other organ sites, such as the ileum and kidneys.
T86 2135-2261 Sentence denotes Understanding the role of non-pulmonary myeloid cells in tissue-specific pathology associated with COVID-19 will be important.
T87 2263-2330 Sentence denotes Prior Knowledge from SARS-CoV-1, MERS-CoV, and Murine Coronaviruses
T88 2331-2539 Sentence denotes While data on COVID-19 patients continues to rapidly emerge, studies of myeloid cell dysfunction in SARS-CoV-1 and MERS-CoV can provide an important roadmap to understanding COVID-19 pathogenesis (Figure 2 ).
T89 2540-2682 Sentence denotes SARS-CoV-1 infection in mouse models results in an aberrant AM phenotype that limits DC trafficking and T cell activation (Zhao et al., 2009).
T90 2683-2834 Sentence denotes Additionally, YM1+ FIZZ1+ alternative macrophages can increase airway hypersensitivity, thus exacerbating SARS-associated fibrosis (Page et al., 2012).
T91 2835-3146 Sentence denotes Further, as described above, murine SARS-CoV-1 studies have demonstrated that delayed IFN-I signaling and inflammatory monocytes-macrophages promote lung cytokine and chemokine levels, vascular leakage, and impaired antigen-specific T cell responses, culminating in lethal disease (Channappanavar et al., 2016).
T92 3147-3358 Sentence denotes The role played by prominent IFN-producing pDCs in SARS-CoV-2 control or pathogenesis warrants investigation, as they have been shown to be critical in murine CoV (MHV) control (Cervantes-Barragan et al., 2007).
T93 3359-3710 Sentence denotes Longitudinal studies in SARS-CoV-2 models are awaited, but initial phenotypic studies in humanized hACE2 mice have shown the characteristic alveolar interstitial pneumonia, with infiltration of lymphocytes and monocytes and accumulation of macrophages in the alveolar lumen (Bao et al., 2020a), which recapitulates patient findings (Xu et al., 2020c).
T94 3711-4074 Sentence denotes Lastly, non-human primate (NHP) studies and patient data on SARS-CoV-1 have also shown that virus spike-specific immunoglobulin G (IgG) responses can exacerbate acute lung injury due to repolarization of alveolar macrophages into proinflammatory phenotypes and enhanced recruitment of inflammatory monocyte via CCL2 and IL-8 (Clay et al., 2012, Liu et al., 2019).
T95 4075-4189 Sentence denotes However, the extent to which the antibody response contributes to disease pathophysiology remains to be confirmed.
T96 4190-4283 Sentence denotes Figure 2 SARS-CoV-2 Infection Results in Myeloid Cell Activation and Changes NK Cell Function
T97 4284-4377 Sentence denotes Based on data from preliminary COVID-19 studies and earlier studies in related coronaviruses.
T98 4378-4606 Sentence denotes IL-6, IL-1β, and IFN-I/III from infected pulmonary epithelia can induce inflammatory programs in resident (alternate) macrophages while recruiting inflammatory monocytes, as well as granulocytes and lymphocytes from circulation.
T99 4607-4699 Sentence denotes Sustained IL-6 and TNF-ɑ by incoming monocytes can drive several hyperinflammation cascades.
T100 4700-4822 Sentence denotes Inflammatory monocyte-derived macrophages can amplify dysfunctional responses in various ways (listed in top-left corner).
T101 4823-4960 Sentence denotes The systemic CRS- and sHLH-like inflammatory response can induce neutrophilic NETosis and microthrombosis, aggravating COVID-19 severity.
T102 4961-5057 Sentence denotes Other myeloid cells, such as pDCs, are purported to have an IFN-dependent role in viral control.
T103 5058-5121 Sentence denotes Monocyte-derived CXCL9/10/11 might recruit NK cells from blood.
T104 5122-5282 Sentence denotes Preliminary data suggest that the antiviral function of these NK cells might be regulated through crosstalk with SARS-infected cells and inflammatory monocytes.
T105 5283-5330 Sentence denotes Dashed lines indicate pathways to be confirmed.
T106 5331-5593 Sentence denotes Arg1, arginase 1; iNOS, inducible-nitric oxide synthase; Inflamm., inflammatory; Mono., monocytes; Macs, macrophages; Eosino, eosinophils; Neutro, neutrophils; NETosis, neutrophil extracellular trap cell death; SHLH, secondary hemophagocytic lymphohistiocytosis.
T107 5595-5648 Sentence denotes Myeloid Cells Contribution to Pathogenic Inflammation
T108 5649-5837 Sentence denotes The initial mode of viral pathogen-associated signal (PAMP) recognition by innate cells has a major impact on downstream myeloid signaling and cytokine secretion (de Marcken et al., 2019).
T109 5838-6220 Sentence denotes While macrophages are somewhat susceptible to MERS-CoV and SARS-CoV-1 infection (Perlman and Dandekar, 2005, Zhou et al., 2014), data do not suggest that they are infected by SARS-CoV-2, although one study reported ACE2 and SARS-CoV-2 nucleocapsid protein is expressed in lymph nodes and spleen-associated CD169+ macrophages of COVID-19 patients producing IL-6 (Chen et al., 2020h).
T110 6221-6414 Sentence denotes Significantly elevated systemic levels of proinflammatory cytokine IL-6 have been reported in several COVID-19 patient cohorts and shown to correlate with disease severity (Mehta et al., 2020).
T111 6415-6562 Sentence denotes Increased IL-6 can also be associated with higher levels of IL-2, IL-7, IFN-ɣ, and GM-CSF, as seen in secondary hemophagocytic lymphohistiocytosis.
T112 6563-6843 Sentence denotes In response to viral infections, MNPs drive IL and IFN-I and IFN-III production resulting in inflammasome activation, induction of pathogenic Th1 and Th17 cell responses, recruitment of effector immune cells, and CRS pathology (Prokunina-Olsson et al., 2020, Tanaka et al., 2016).
T113 6844-7074 Sentence denotes Independently, in vitro studies have demonstrated SARS-CoV-1 infection can induce intracellular stress pathways, resulting in NLRP3-dependent inflammasome activation and macrophage pyroptosis (Chen et al., 2019, Shi et al., 2019).
T114 7075-7287 Sentence denotes Functional studies are required to implicate these myeloid inflammasome pathways in COVID-19 lung pathology and to assess other immunogenic pathways such as RIPK1/3-dependent necroptosis (Nailwal and Chan, 2019).
T115 7288-7452 Sentence denotes In conclusion, the strength and duration of myeloid ISG)signaling potentially dictate COVID-19 disease severity, but rigorous studies are warranted to confirm this.
T116 7453-7658 Sentence denotes Lastly, more work is needed to ascertain the mechanistic role played by lung-resident and recruited granulocytes in SARS-CoV-2 control and pathogenesis (Camp and Jonsson, 2017, Flores-Torres et al., 2019).
T117 7659-7901 Sentence denotes In contrast to their early protective role, neutrophil NETosis and macrophage crosstalk can drive later-stage inflammatory cascades (Barnes et al., 2020), underscoring the overall pathogenic nature of damage-sensing host responses (Figure 2).
T118 7902-8141 Sentence denotes Collectively, the current knowledge of CoVs and SARS-CoV-2 infection, in particular, points to an inadvertent collusion involving myeloid cells in COVID-19 pathogenesis, despite their critical role in early sensing and antiviral responses.