PONE-D-24-51638IL-18 production is required for the generation of a Th1 response during chromoblastomycosisPLOS ONE

Dear Dr. Almeida,

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PLOS ONE

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Additional Editor Comments:

Major Revision Requested

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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

Reviewer #2: Partly

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #2: Yes

Reviewer #3: Yes

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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: Methodology:

Please include a subitem showing the macrophage obtention from BMDM.

correct this statement: intraperitoneal (i.p.) injection of 1 ml of PBS without (the control) or with 2 x 107

It seems that it is unclear to the reader if all experiments were conducted on all types of animals.

Results:

The first result does not mention the mice strain that the macrophages came from as well as the other results.

A better results description showing the mice strain used for macrophages assay is important. The graphs need a better description and indication of the cells used from mice strain and the correct pharmacological approach used indicating with or without inhibitor used.

At the present form important results description is missing.

Reviewer #2: The authors conducted a study with wild mice and mice individually knocked out for NLRP3, IFN-γ, Caspase-1/-11, or IL-18 to verify the role of IL18 and NLRP3 inflammasome in experimental chromoblastomycosis.

The title of the paper should be modified to IL-18 production is required for the generation of a Th1 response during experimental chromoblastomycosis.

The methods are appropriate to achieve the proposed objectives. However, the comparative evaluation of fungal quantification was obtained by counting colony-forming units (CFU) in macerates, liver, and spleen. I suggest that the authors also provide information about the aspects and compare the inflammatory reactions in the liver and spleen of both groups of animals.

Authors must explain what they understand by severe forms of chromoblastomycosis (see page 3, second line of the penultimate paragraph and page 9 - second and third lines of the first paragraph) since in human disease this mycosis usually affects the skin and subcutaneous tissue and rarely manifests as systemic disease. Insert the reference(s) in the first paragraph of page 9.

Insert the reference of the several papers mentioned in the last paragraph of page 9.

Page 15 - Figure 2 caption - Why do the authors classify it as deep chromoblastomycosis? In this model, there is visceral involvement (liver and spleen), therefore systemic disease.

In the conclusion section, the authors should state that their work demonstrates, for the first time, the involvement of immune mechanisms mediated by the NRLP3 inflammasome in experimental chromoblastomycosis.

Reviewer #3: This is an interesting research that demonstrates the role of IL18 in the activation of Th1 response to control chromoblastomycosis infection. Although the expressive presence of such cytokine in human tissue have been previously demonstrated, the direct evidence and interaction in the context of NLRP3 and caspase1 is new.

The last part of page 8, and first topic on page 9 fit better in discussion. In this last one, when considered IFN-gamma, which patients? Is it part of the present research or, maybe it could fit better in discussion?

Page 18, second paragraph, correct NLRP3, not nlrp.

How could authors explain the similar expression of IL10 and IL12?

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes:  Carla Pagliari

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IL-18 production is required for the generation of a Th1 response during experimental chromoblastomycosis

PONE-D-24-51638R1

Dear Dr. Almeida,

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,

Divakar Sharma, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Accept

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

Reviewer #2: 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

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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

Reviewer #2: 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

Reviewer #2: 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: The authors provided the answers adequately.

I think the manuscript can be accepted for publication.

Thank you for this opportunity.

Reviewer #2: The authors responded and answered the questions appropriately. Nothing more to comment.

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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: No

Reviewer #2: Yes:  Mirian Nacagami Sotto

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