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

Montes de Oca, M.; Dey, S.; Van Bocxlaer, K.; 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.

doi:10.1101/2023.02.03.526940

bioRxiv · 10.1101/2023.02.03.526940

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

Montes de Oca, M.·Dey, S.·Van Bocxlaer, K.·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.

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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 IFN{gamma}+ 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. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/526940v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1238cbaorg.highwire.dtl.DTLVardef@ec350eorg.highwire.dtl.DTLVardef@18f412corg.highwire.dtl.DTLVardef@1ffd468_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Montes de Oca, M., Dey, S., Van Bocxlaer, K., 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.. 2023-02-03. UVB modifies skin immune-stroma cross-talk and promotes effector T cell recruitment during cryptic Leishmania donovani infection. https://doi.org/10.1101/2023.02.03.526940

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