Plasmacytoid dendritic cells during COVID-19: Ally or adversary?

Sluis, Renée M. van der; Holm, Christian K.; Jakobsen, Martin R.

doi:10.1016/j.celrep.2022.111148

Cited by 20 publications

(14 citation statements)

References 208 publications

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“…LD2 distinguished both the nS and vS groups based on IL6 signaling, oxidative phosphorylation, and inflammatory responses from the nM and HD groups. Similarly, LD1 in pDCs showed that the vS group is more enriched with cell cycle-related signature such as G2M checkpoint and E2F targets; in contrast, in LD2, transciptional signatures of pDCs from COVID-19 patients were enriched with inflammatory response, IL6 signaling and, interferon-gamma responses, consistent with other studies ( 26 , 37 ) ( Figures 3C, D ). In addition, to further illustrate the detailed differences among the nM, nS, and vS groups when compared with HD groups, we visualized the DEGs as heatmaps and also performed a canonical computational pathway analysis by IPA.…”

Section: Resultssupporting

confidence: 90%

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Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses

Sun

Gao²,

Zhao³

et al. 2022

Front. Immunol.

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SARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19. However, the effects of viremia on immune responses in blood cells remain unclear. The current study comprehensively examined transcriptional signatures of PBMCs involving T cells, B cells, NK cells, monocytes, myeloid dendritic cells (mDCs), and plasmacytoid dendritic cells (pDCs) respectively, from three different groups including individuals with moderate (nM), or severe disease with (vS) or without (nS) detectable plasma viral load. Whole transcriptome analysis demonstrated that all seven immune cell subsets were associated with disease severity regardless of cell type. Supervised clustering analysis demonstrated that mDCs and pDCs gene signatures could distinguish disease severity. Notably, transcriptional signatures of the vS group were enriched in pathways related to DNA repair, E2F targets, and G2M checkpoints; in contrast, transcriptional signatures of the nM group were enriched in interferon responses. Moreover, we observed an impaired induction of interferon responses accompanied by imbalanced cell-intrinsic immune sensing and an excessive inflammatory response in patients with severe disease (nS and vS). In sum, our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in seven major immune cells in COVID-19 patients.

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Section: Resultssupporting

confidence: 90%

“…In addition, recent studies also showed that infected circulating monocytes can induce acute inflammatory responses and cause cytokine storm, tissue-damage, and cell death ( 25 ). Furthermore, a recent study has shown that pDCs are resistant to SARS-CoV-2 infection but can be efficiently activated by the virus ( 26 , 27 ).…”

Section: Introductionmentioning

confidence: 99%

Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses

Sun

Gao²,

Zhao³

et al. 2022

Front. Immunol.

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“…3b). pDC are dominant producers of type I interferons (IFNs) during SARS-CoV-2 infection, with low numbers of pDCs and low type I IFN levels generally associated with increased COVID-19 severity (Contoli et al, 2021; Van der Sluis et al, 2022).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, the clearly depressed phagocytosis signatures, the identification of multiple annotations associated with modulated macrophage responses (with macrophages the key mediators of efferocytosis), and the overall lack of detectable changes to adaptive immune responses, might be viewed as consistent with a role for dysregulated phagocytosis/efferocytosis (Ge et al, 2022; Razi et al, 2023). Reduced phagocytosis of SARS-CoV-2 infected cells at 2 dpi might reduce M1 macrophage activation, subsequent pDC activation (Garcia-Nicolas et al, 2023), and the ensuing cytokine responses (Severa et al, 2021; Van der Sluis et al, 2022). Less phagocytosis at the peak of infection might also lead to more secondary necrosis and/or necroptosis of SARS-CoV-2 infected cells, thereby promoting inflammation at 6 dpi (Fredman et al, 2023; Li et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Bishop,

Yan,

Nguyen

et al. 2023

Preprint

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Global microplastic (MP) pollution is now well recognized, with humans and animals consuming and inhaling MPs on a daily basis. Herein we described the effects of azide-free, 1 µm polystyrene MP beads co-delivered into lungs with a SARS-CoV-2 omicron BA.5 inoculum using a mouse model of mild COVID-19. Lung virus titres and viral RNA levels were not significantly affected by MPs, with overt clinical or histopathological changes also not observed. However, RNA-Seq of infected lungs revealed that MP exposure suppressed innate immune responses at 2 days post infection (dpi) and increased pro-inflammatory signatures at 6 dpi. The cytokine profile at 6 dpi showed a significant correlation with the ‘cytokine release syndrome’ signature seen in some severe COVID-19 patients. This study adds to a growing body of literature suggesting that MPs can dysregulate inflammation in specific disease settings.Graphical AbstractHIGHLIGHTSA single inoculation of microplastics dysregulated SARS-CoV-2 lung inflammationAt the peak of SARS-CoV-2 infection microplastics decreased early innate responsesLater post infection microplastics promoted a “cytokine release syndrome” signatureA key mechanism may involve the inhibition of the phagocytosis of infected cellsAzide-free microplastics were used, with no elevated ROS responses identifiedPostulated mechanisms whereby microplastics might decrease the proinflammatory responses 2 days after SARS-CoV-2 infection, yet promote the proinflammatory ‘cytokine release syndrome’ signature at 6 days post infection.

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“…The deconvolution results for Nanostring data (Figure S1f) also show that ROIs labelled as bronchial epithelium and T2 contain a high proportion of epithelial cells. Additionally, we found that COVID‐affected ROIs show a high proportion of plasmacytoid dendritic cells (pDC) and macrophages, suggesting a COVID‐19 induced cytokine storm [20–22]. While CD8 T cells were significantly higher in COVID‐19 samples based on PhenoImager HT data, this difference was not apparent in the GeoMx data (although the median gene expression value for relevant markers was indeed higher in COVID‐19 samples) (Figure S1g–i).…”

Section: Resultsmentioning

confidence: 99%

A robust platform for integrative spatial multi‐omics analysis to map immune responses to SARS‐CoV‐2 infection in lung tissues

Tan,

Grice,

Tran

et al. 2023

Immunology

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The SARS‐CoV‐2 (COVID‐19) virus has caused a devastating global pandemic of respiratory illness. To understand viral pathogenesis, methods are available for studying dissociated cells in blood, nasal samples, bronchoalveolar lavage fluid and similar, but a robust platform for deep tissue characterization of molecular and cellular responses to virus infection in the lungs is still lacking. We developed an innovative spatial multi‐omics platform to investigate COVID‐19‐infected lung tissues. Five tissue‐profiling technologies were combined by a novel computational mapping methodology to comprehensively characterize and compare the transcriptome and targeted proteome of virus infected and uninfected tissues. By integrating spatial transcriptomics data (Visium, GeoMx and RNAScope) and proteomics data (CODEX and PhenoImager HT) at different cellular resolutions across lung tissues, we found strong evidence for macrophage infiltration and defined the broader microenvironment surrounding these cells. By comparing infected and uninfected samples, we found an increase in cytokine signalling and interferon responses at different sites in the lung and showed spatial heterogeneity in the expression level of these pathways. These data demonstrate that integrative spatial multi‐omics platforms can be broadly applied to gain a deeper understanding of viral effects on cellular environments at the site of infection and to increase our understanding of the impact of SARS‐CoV‐2 on the lungs.

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Plasmacytoid dendritic cells during COVID-19: Ally or adversary?

Cited by 20 publications

References 208 publications

Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses

Immune-profiling of SARS-CoV-2 viremic patients reveals dysregulated innate immune responses

Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

A robust platform for integrative spatial multi‐omics analysis to map immune responses to SARS‐CoV‐2 infection in lung tissues

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