https://orcid.org/0000-0002-5710-2839
Peer Review History
| Original SubmissionJuly 14, 2023 |
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Dear Prof. Geijtenbeek, Thank you very much for submitting your manuscript "SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and by several independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Jacob S. Yount Academic Editor PLOS Pathogens Alexander Gorbalenya Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Reviewer's Responses to Questions Part I - Summary Please use this section to discuss strengths/weaknesses of study, novelty/significance, general execution and scholarship. Reviewer #1: In this study, van de Donk and colleagues obtained several lines of evidence that strongly suggest that SARS-CoV-2 suppresses TLR4, the major bacterial TLR on human DCs and that SARS-CoV-2 interacts with DC-SIGN leading to Raf-1-mediated suppression of TLR4 signaling crucial in the defense against bacterial infections. The paper is well written, data well oresented, and most importantly interesting. Reviewer #2: In this manuscript, van der Donk et al. investigate dendritic cell (DC) function after SARS-CoV-2 exposure, following up on their earlier study (van der Donk et al. (2022) Eur. J. Immunol.) showing that SARS-CoV-2 does not activate extracellular TLRs or induce DC maturation. Here, they first show that dendritic cell exposure to SARS-CoV-2 spike protein dampens responsiveness to lipopolysaccharide (LPS), a TLR4 agonist, but not the response to TLR2/6 or TLR3 agonists. After confirming previous literature that the SARS-CoV-2 spike protein binds to the C-type lectin receptor DC-SIGN, they show that blocking DC-SIGN on dendritic cells appears to restore the response to LPS in DCs pre-exposed to SARS-CoV-2 spike protein or authentic virus. Finally, Raf-1 inhibition similarly restored some of the responsiveness to LPS in DCs pre-exposed to SARS-CoV-2, supporting earlier findings where activation of DC-SIGN by bacterial or viral ligands was shown to modulate TLR4 signaling via Raf-1 (e.g. Gringuis et al. (2009) Nat. Immunol.). Overall, the manuscript presents interesting data and addresses an important topic (bacterial co-infection in the context of COVID-19). The study is carefully executed and the data are interpreted appropriately. However, it is a fairly minor conceptual advance compared to previous work. In my opinion, further mechanistic studies (see comment 1 below) would make the manuscript more suitable for publication in PLoS Pathogens. ********** Part II – Major Issues: Key Experiments Required for Acceptance Please use this section to detail the key new experiments or modifications of existing experiments that should be absolutely required to validate study conclusions. Generally, there should be no more than 3 such required experiments or major modifications for a "Major Revision" recommendation. If more than 3 experiments are necessary to validate the study conclusions, then you are encouraged to recommend "Reject". Reviewer #1: (No Response) Reviewer #2: 1. In the previous study by this group, it was shown that stimulation of DC-SIGN with HIV-1 enhanced LPS-induced cytokine expression (e.g. Gringuis et al. (2009) Nat. Immunol.), whereas here, SARS-CoV-2 dampens the LPS-induced cytokine response. What underlies this difference? 2. In Figure 3, the authors evaluate IL-8 expression in 293T/TLR4 cells, while IFN-beta, IL-6, IP-10, IL-10, etc. (and not IL-8) are evaluated in other figures. It would be good to also confirm in Figure 3 that the levels of one of the cytokines (e.g., IP-10, IL-6, IL-10) that exhibit decreased responsiveness to LPS after SARS-CoV-2 exposure in DCs is not decreased in the 293T/TLR4 cell model, to strengthen the conclusion that indeed the effect seen in DCs is not due to a direct interaction between SARS-CoV-2 and TLR4. 3. In Figure 4A, would recommend including an isotype control antibody. ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: (No Response) Reviewer #2: 1. Related to Figure 6, it is appreciated that the statistical analysis is clear in the figures as well as often noted in the text. The donor variance is commented upon. Even so, it is important to note in lines 136-138 that although cytokines levels appear restored with anti-DC-SIGN antibody treatment, this is only significant for IP10 and IL-6. The same goes for lines 140-143 regarding the effect of Raf-1 inhibition. ********** PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here on PLOS Biology: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. 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| Revision 1 |
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Dear Prof. Geijtenbeek, We are pleased to inform you that your manuscript 'SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN' has been provisionally accepted for publication in PLOS Pathogens. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Jacob S. Yount Academic Editor PLOS Pathogens Alexander Gorbalenya Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Prof. Geijtenbeek, We are delighted to inform you that your manuscript, "SARS-CoV-2 suppresses TLR4-induced immunity by dendritic cells via C-type lectin receptor DC-SIGN," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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