https://orcid.org/0000-0002-5722-1109
Peer Review History
| Original SubmissionNovember 17, 2020 |
|---|
|
Dear Dr. Bosinger, Thank you very much for submitting your manuscript "Tissue-specific transcriptional profiling of plasmacytoid dendritic cells reveals a hyperactivated state in chronic SIV infection" 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, Daniel C. Douek Associate Editor PLOS Pathogens Richard Koup 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 their manuscript, Lee and colleagues perform a cross-NHP species transcriptomic analysis of pDCs to evaluate their role(s) in ongoing HIV-induced immune activation. The investigator’s conclude in the pathogenic rhesus species, pDCs develop a hyperactivated state in lymph nodes during SIV infection. The study is mostly well done and very well-written, but there are some experimental and interpretive concerns that should be addressed. Reviewer #2: Lee et al studied pDC in SIV rhesus macaque infection to further understand their role. They find that pDC appear to be recruited to lymph nodes during infection and have an enhanced activation state as demonstrated by RNA-seq. The authors claim that the pDC are driving T cell activation and exhaustion, although this is not formally demonstrated in functional assays. Data are shown that confirm that pDC are major IFNa producers. The authors also suggest that pDCs themselves are exhausted. It is unclear to this reviewer whether they are indicating that pDC in blood are exhausted or those both in LN and blood. If the pDC in LN in blood are exhausted, then why is IFNa being produced. This needs to be clarified. The manuscript has used RNA-seq technology to further delineate the role of pDC in SIV (and thus test in HIV) infection. This methodology may allow easier investigation of such a difficult to study cell population ex vivo. ********** 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: The SMs were clearly infected much longer than rhesus. How was this evaluated as a potential confounding factor? It may be difficult to make a direct comparison at all here. A similar question applies for the fact that the SMs were likely much much older than the rhesus used. This could have a major impact on ISG and other gene expression and should be clarified for the infected and uninfected animals in both species. This may also require some additional analyses. It is unclear to this reviewer, how it was determined these are tissue-resident pDCs in LN, rather than pDC that may have migrated there or are blood contaminating. This should be rephrased unless specific confirmation of tissue-residency markers (CD69, CD49s, etc) were used. This does not undermine the disparate profiles of LN vs. circulating pDC, but given recent changes in how tissue-resident populations are identified, wording should be careful. It would also be useful to confirm IFN production in the peripheral and LN pDCs by ICS or ELISPOT or ELISA to verify the conclusions by transcripts. Were ISGs in non-pDCs upregulated correlating within pDCs? Since the pDC may be a primary source this would seem a natural analysis rather than necessarily looking at ISGs in the pDCs themselves. The authors make the argument that hyperactivated pDCs may have a role in lentivirus disease. Were no virologic measurements performed? Particularly in LN. Reviewer #2: No functional data is shown that pDC are indeed exhausted or whether they drive exhaustion of other cell types. ********** 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: Clarify if the macaques in figure one that are SIV infected are on cART or not. Please add the p value for the uninfected counterparts on line 347, and in line 359 Fig 3d, please show error bars. Also In fig 3 Lee et al shows shows constitutive expression in infected animals of RNA, is this true for protein expression?, this condition could be added in fig 3d, ie add pdc from uninfected animals at the same concentration without stimulation. Do we know whether the pDC in LN versus PB or both contain SIV virus as others have shown? If so, can this explain some of the findings? Is it confirmed that pDC in one compartment are CCR7 surface positive in one compartment over another? TIM-3 has been associated with pdC exhaustion in mice and humans, what was TIM-3 levels in these pDCs. Exhaustion markers TIGIT is elevated in pdC from SIV infected animals but this reviewer does not see expression of pDC from uninfected animals. In fig 5c, it is unclear whether the pDC are from periphery or LN. ********** 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. Reproducibility: To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plospathogens/s/submission-guidelines#loc-materials-and-methods |
| Revision 1 |
|
Dear Dr. Bosinger, We are pleased to inform you that your manuscript 'Tissue-specific transcriptional profiling of plasmacytoid dendritic cells reveals a hyperactivated state in chronic SIV infection' 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, Daniel C. Douek Associate Editor PLOS Pathogens Richard Koup 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): 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: (No Response) Reviewer #2: confirms pDCs are inducing activation in this model ********** 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: (No Response) ********** 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: (No Response) ********** 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 |
| Formally Accepted |
|
Dear Dr. Bosinger, We are delighted to inform you that your manuscript, "Tissue-specific transcriptional profiling of plasmacytoid dendritic cells reveals a hyperactivated state in chronic SIV infection," 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 |
Open letter on the publication of peer review reports
PLOS recognizes the benefits of transparency in the peer review process. Therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. Reviewers remain anonymous, unless they choose to reveal their names.
We encourage other journals to join us in this initiative. We hope that our action inspires the community, including researchers, research funders, and research institutions, to recognize the benefits of published peer review reports for all parts of the research system.
Learn more at ASAPbio .