PONE-D-21-17024

Estradiol - induced immune suppression via prostaglandin E2 during parturition in bovine leukemia virus-infected cattle

PLOS ONE

Dear Dr. Konnai,

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Academic Editor

PLOS ONE

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3. You indicated that you had ethical approval for your study. In your Methods section, please ensure you have also stated whether you obtained consent from owners of the cattle included in the study or whether the research ethics committee or IRB specifically waived the need for their consent.

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript addresses a very important need for better definition of factors that impact immunosuppression in the peripartum period. The focus on PGE2 and estradiol is an important consideration and has yielded insight on specific receptor involvement.However, it is unclear if the focus is on at the time of parturition or the surrounding period?. The outcomes that determined specific conclusion on the selected term eg effect at parturition for the observed effects are not clear. More information on age, stage of lactation, parity, breed, diet and management etc would help uncover other possible contributing factors and should at least be discussed. Furthermore, the possible contribution of declining progesterone concentration (known immunosuppressant) and health parameters such status of infection by other pathogens, occurrence of diseases such as laminitis, mastitis etc. are not considered. In light of the impact of LPS on in vitro COX2 expression and PGE2 secretion what were the levels of endotoxins in reagents and containers for in vitro studies and what controls were used to evaluate the possible contribution of LPS? Discuss the use of the DMSO control versus buffer or known plasma. Please check sentence structure/missing words etc. eg line 2 and line 12.1, Not clear what this sentence means please edit Line 2 In dairy cattle, efficient milk production continues to require for pregnancy and 3 parturition each year.

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Reviewer #1: Yes: Mulumebet Worku

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Estradiol - induced immune suppression via prostaglandin E2 during parturition in bovine leukemia virus-infected cattle

PONE-D-21-17024R1

Dear Dr. Konnai,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Juan J Loor

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for your response. I would like to encourage follow up studies to uncover contributing factors for improved management decsions and translational applications.

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7. 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: Yes: Mulumebet Worku