UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection

Marcela Montes de Oca; Shoumit Dey; Katrien Van Bocxlaer; Helen Ashwin; Najmeeyah Brown; Elmarie Myburgh; Nidhi S Dey; Gulab Fatima Rani; Edward Muscutt; Mohamed Osman; Damian Perez-Mazliah; Sally James; Lesley Gilbert; Mitali Chatterjee; Paul M Kaye

doi:10.1101/2023.02.03.526940

UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection

Marcela Montes de Oca, Shoumit Dey, Katrien Van Bocxlaer, Helen Ashwin, Najmeeyah Brown, Elmarie Myburgh, Nidhi S Dey, Gulab Fatima Rani, Edward Muscutt, Mohamed Osman, Damian Perez-Mazliah, Sally James, Lesley Gilbert, Mitali Chatterjee, Paul M Kaye

Research output: Working paper

Abstract

Many parasites of significant public health importance assume skin residency without causing overt pathlogy. How immune and stromal cells respond to such “cryptic” infections and how exposure to UVB alters such responses in poorly understood. We combined scRNA-seq, spatial transcriptomics and inferential network analysis to address these questions in a model of cryptic skin infection by Leishmania donovani. In infected C57BL/6 mice, p-selectin and CXCL12 interactions dominate intercellular communication between leucocytes, fibroblast and endothelial cells, but effector T cell function remains muted. Following UVB exposure, increased numbers of IFNγ+ CD4+ Th1 cells and NK cells enter the skin, communicating with stromal cells via CCL5-CCR5 and LFA-1-ICAM1/2. However, spatial mapping indicated that Th1 cells and macrophages occupied distinct niches after UVB exposure, likely limiting effector function. Our data provide the first holistic view of the immune landscape during cryptic L. donovani infection and demonstrate how UVB exposure fundamentally reshapes this response.Competing Interest StatementThe authors have declared no competing interest.

Original language	English
Publisher	bioRxiv, at Cold Spring Harbor Laboratory
Number of pages	44
DOIs	https://doi.org/10.1101/2023.02.03.526940
Publication status	Published - 3 Jan 2023

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10.1101/2023.02.03.526940Licence: CC BY

http://biorxiv.org/content/early/2023/02/03/2023.02.03.526940.abstract

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Oca, M. M. D., Dey, S., Bocxlaer, K. V., Ashwin, H., Brown, N., Myburgh, E., Dey, N. S., Rani, G. F., Muscutt, E., Osman, M., Perez-Mazliah, D., James, S., Gilbert, L., Chatterjee, M., & Kaye, P. M. (2023). UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection. bioRxiv, at Cold Spring Harbor Laboratory. https://doi.org/10.1101/2023.02.03.526940

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title = "UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection",

abstract = "Many parasites of significant public health importance assume skin residency without causing overt pathlogy. How immune and stromal cells respond to such “cryptic” infections and how exposure to UVB alters such responses in poorly understood. We combined scRNA-seq, spatial transcriptomics and inferential network analysis to address these questions in a model of cryptic skin infection by Leishmania donovani. In infected C57BL/6 mice, p-selectin and CXCL12 interactions dominate intercellular communication between leucocytes, fibroblast and endothelial cells, but effector T cell function remains muted. Following UVB exposure, increased numbers of IFNγ+ CD4+ Th1 cells and NK cells enter the skin, communicating with stromal cells via CCL5-CCR5 and LFA-1-ICAM1/2. However, spatial mapping indicated that Th1 cells and macrophages occupied distinct niches after UVB exposure, likely limiting effector function. Our data provide the first holistic view of the immune landscape during cryptic L. donovani infection and demonstrate how UVB exposure fundamentally reshapes this response.Competing Interest StatementThe authors have declared no competing interest.",

author = "Oca, {Marcela Montes de} and Shoumit Dey and Bocxlaer, {Katrien Van} and Helen Ashwin and Najmeeyah Brown and Elmarie Myburgh and Dey, {Nidhi S} and Rani, {Gulab Fatima} and Edward Muscutt and Mohamed Osman and Damian Perez-Mazliah and Sally James and Lesley Gilbert and Mitali Chatterjee and Kaye, {Paul M}",

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Oca, MMD , Dey, S , Bocxlaer, KV, Ashwin, H, Brown, N , Myburgh, E , Dey, NS, Rani, GF, Muscutt, E, Osman, M , Perez-Mazliah, D , James, S, Gilbert, L, Chatterjee, M & Kaye, PM 2023 'UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection' bioRxiv, at Cold Spring Harbor Laboratory. https://doi.org/10.1101/2023.02.03.526940

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AU - Ashwin, Helen

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