PPATHOGENS-D-26-00450

Homotypic interactions between SLAMF1 receptors on innate T cells and neutrophils regulate killing of fungi

PLOS Pathogens

Dear Dr. Wuthrich,

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Amariliz Rivera

Academic Editor

PLOS Pathogens

Michal Olszewski

Section Editor

PLOS Pathogens

Sumita Bhaduri-McIntosh

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0003-2946-9497

Michael Malim

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0002-7699-2064

Additional Editor Comments :

The current study provides convincing data to support the conclusions presented. The findings are of interest to a broad audience and will open new areas for investigation. Please address the reviewer's recommendations to modify the text.

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Reviewers' Comments:

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 report, Lau et al. describe how SLAMF1 governs homotypic interactions between CD4+ T cells and neutrophils to enhance their antifungal killing capacity during infection with Blastomyces dermatitidis (Bd). The study uses a well-rounded approach with multiple cell-type-specific SLAMF1 KO mice, in vivo and in vitro assays of fungal killing and assays of inter-cellular communications to arrive at the conclusions, which are well supported by the data. Overall, the manuscript is well written and provides an important advance in the field of antifungal immunity by identifying inter-cellular communication in mediating fungal clearance.

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Part II – Major Issues: Key Experiments Required for Acceptance

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Reviewer #1: 1. The presented data convincingly show the role of SLAMF1 in phagocytic fungal killing. Do the authors see any role for SLAMF1 in leukocyte accumulation/recruitment

2. The authors focus their attention on neutrophils as there were ~4-fold higher number of neutrophils associated with the fungus than monocytes. While this is reasonable, as monocytes also participate in fungal killing and harbor SLAMF1, does a similar homotypic interaction-mediated enhancement of killing is observed for monocytes too?

3. Does the absence of SLAMF1 on CD4 T cells lead to impaired host survival?

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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: 1. In Figure 1C, the labels hide the flow events on the plot. Please modify the label position so that the events are visible.

2. The mouse fungal challenge method should include additional details on route of administration, and how lungs were homogenized.

3. For the in vitro killing assay, please specify the effector-to-target ratios used for the ease of interpretation.

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Reviewer #1: No

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Dear Dr. Wuthrich,

We are pleased to inform you that your manuscript 'Homotypic interactions between SLAMF1 receptors on innate T cells and neutrophils regulate killing of fungi' has been provisionally accepted for publication in PLOS Pathogens.

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Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens.

Best regards,

Amariliz Rivera

Academic Editor

PLOS Pathogens

Michal Olszewski

Section Editor

PLOS Pathogens

Sumita Bhaduri-McIntosh

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0003-2946-9497

Michael Malim

Editor-in-Chief

PLOS Pathogens

orcid.org/0000-0002-7699-2064

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Reviewer Comments (if any, and for reference):