PONE-D-23-13337Indoor aeroallergens from American cockroaches and mites initiate atopic march via cutaneous contact in a murine modelPLOS ONE

Dear Dr. Wang,

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Additional Editor Comments:

This is an intriguing study that makes a contribution to the literature on atopic march. You will see that the expert reviewers have provided a favorable position on your study and provided important criticisms. I agree with their assessment. The reviewer points should be addressed in a revision. I look forward to the submission of your revised manuscript.

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Reviewers' comments:

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

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Reviewer #1: This is an interesting manner to study the atopic march, and the rationale for studying cockroach and HDM allergens is sound. My main question is - How did the authors decide to patch the mice for 3 one week exposures versus a different method? What is the justification for performing the experiment this way?

I would discuss the significance of the IgE and IgG results further.

Line 41 – should be “increase” instead of “increased”

The sentence that starts in line 55 has confusing wording. Perhaps take out “it described a typical clinical feature that” and start the sentence with, “Patients begin with atopic dermatitis…”

Line 183 – “IL-10” is mentioned twice in a row

Line 233 – “in the” should be in the sentence - “known to participate in the progression of AD”.

Line 238 – Should be “shown”, not “showed”

Line 247 – I believe the authors meant to write “epidermal” instead of “epithermal”

Other than what is outlined above, there are some sentences that could be worded better as they are incomplete or lacking.

Reviewer #2: In this study, a mouse model was used to show that epicutaneous sensitization to aeroallergens also led to nasal and airway symptoms comparable to atopic march as described in humans. The approach used was appropriate and the results are interesting. However, there are several points about the hypothesis and the project design that should be noted.

1. It is curious how similar is this model when compared to the situation in humans. As we know, there is a significant time gap in human atopic march. The immediate nasal and airway symptoms triggered by the epicutaneous sensitization in this mouse model is somehow deviated from what we expected.

2. A single dose of CraA, rPer a 2 and rDer p2 has been used for epicutaneous sensitization. How could this dose be justified? Moreover, no dose-dependent effect could be observed if a single dose was used.

3. In this study, PBS was used as the negative control for comparison. However, it is expected that a non-allergic protein should be a better negative control in order to show the sensitization effects of the three agents applied.

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Reviewer #1: No

Reviewer #2: No

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Indoor aeroallergens from American cockroaches and mites initiate atopic march via cutaneous contact in a murine model

PONE-D-23-13337R1

Dear Dr. Wang,

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.

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Sincerely,

Nicholas A. Pullen, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

I have reviewed your changes in response to reviewer minor concerns, and I am happy to endorse the manuscript for publication.

Reviewers' comments: N/A