The timing of natural killer cell response in coronavirus infection: a concise model perspective
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
- @AilisDr's saved articles (AilisDr)
Abstract
Coronaviruses, including SARS-CoV, MERS-CoV, and SARS-CoV-2 cause respiratory diseases with remarkably heterogeneous progression. This in part reflects the viral ability to influence the cytokine secretion and thereby the innate immune system. Especially the viral interference of IFN-I signaling and the subsequent deficiency of innate immune response in the early phase have been associated with rapid virus replication and later excessive immune responses. We propose a mathematical framework to analyze IFN-I signaling and its impact on the interaction motif between virus, NK cells and macrophages. The model recapture divergent dynamics of coronavirus infections including the possibility for elevated secretion of IL-6 and IFN- γ as a consequence of exacerbated macrophage activation. Dysfunction of NK cells recruitment increase disease severity by leading to a higher viral load peak, the possibility for excessive macrophage activation, and an elevated risk of the cytokine storm. Thus the model predicts that delayed IFN-I signaling could lead to pathogenicity in the latter stage of an infection. Reversely, in case of strong NK recruitment from infected cells we predict a possible chronic disease state with moderate and potentially oscillating virus/cytokine levels.
Article activity feed
-
SciScore for 10.1101/2021.08.02.454730: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our model has limitations and should only be seen as a modest step of putting key elements of the innate immune system into a dynamic framework. In particular, we omit the anti-inflammatory cytokines secreted by the macrophages that reduce recruitment of …
SciScore for 10.1101/2021.08.02.454730: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our model has limitations and should only be seen as a modest step of putting key elements of the innate immune system into a dynamic framework. In particular, we omit the anti-inflammatory cytokines secreted by the macrophages that reduce recruitment of macrophages in a previous model of innate immunity [55]. Extension of these next-level cells may reduce and extend the macrophage dynamics to the longer timescales where adaptive immunity also comes into play. The model could be extended further into the disease progression with more components in the immune systems including the role of CD8 T cells. A previous study about the motif comprised of the interactions between antigen and CD8 T cells also suggested that bistability would result from the interplay between antigen and the immune system [56]. It is also interesting to compare our model to the quite different and elaborate model of ref. [57] that follows a population of human cells by assuming that IFN-1 converts infected cells to resistant cells. In that model, the NK cells are the main cause of direct virus elimination, and the macrophages primarily act by inducing IFN-1 that in turn reduce virus proliferation. Despite the substantial differences, the model in ref. [57] contains the central motif of Fig. 2B, leading to similar predictions of increased macrophages activity associated with reduction of IFN-1 signaling. The heterogeneity of the viral kinetics has been discussed in other relevant models in contexts that i...
Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
-
