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Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy

Hematophagous ectoparasites, such as ticks, rely on impaired wound healing for skin attachment and blood feeding. Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to arthropod-borne diseases. Here, we used orthogon...

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Autores principales: Marnin, Liron, Bogale, Haikel N., Laukaitis-Yousey, Hanna J., Valencia, Luisa M., Rolandelli, Agustin, O’Neal, Anya J., Ferraz, Camila Rodrigues, Schmitter-Sánchez, Axel D., Cuevas, Emily Bencosme, Nguyen, Thu-Thuy, Leal-Galvan, Brenda, Rickert, David M., Bruno, Vincent M., Tays Mendes, M., Samaddar, Sourabh, Rainer Butler, L., Singh, Nisha, Cabrera Paz, Francy E., Oliver, Jonathan D., Jameson, Julie M, Munderloh, Ulrike G., Oliva Chávez, Adela S., Mulenga, Albert, Park, Sangbum, Serre, David, Pedra, Joao H.F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659423/
https://www.ncbi.nlm.nih.gov/pubmed/37986907
http://dx.doi.org/10.1101/2023.11.10.566612
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author Marnin, Liron
Bogale, Haikel N.
Laukaitis-Yousey, Hanna J.
Valencia, Luisa M.
Rolandelli, Agustin
O’Neal, Anya J.
Ferraz, Camila Rodrigues
Schmitter-Sánchez, Axel D.
Cuevas, Emily Bencosme
Nguyen, Thu-Thuy
Leal-Galvan, Brenda
Rickert, David M.
Bruno, Vincent M.
Tays Mendes, M.
Samaddar, Sourabh
Rainer Butler, L.
Singh, Nisha
Cabrera Paz, Francy E.
Oliver, Jonathan D.
Jameson, Julie M
Munderloh, Ulrike G.
Oliva Chávez, Adela S.
Mulenga, Albert
Park, Sangbum
Serre, David
Pedra, Joao H.F.
author_facet Marnin, Liron
Bogale, Haikel N.
Laukaitis-Yousey, Hanna J.
Valencia, Luisa M.
Rolandelli, Agustin
O’Neal, Anya J.
Ferraz, Camila Rodrigues
Schmitter-Sánchez, Axel D.
Cuevas, Emily Bencosme
Nguyen, Thu-Thuy
Leal-Galvan, Brenda
Rickert, David M.
Bruno, Vincent M.
Tays Mendes, M.
Samaddar, Sourabh
Rainer Butler, L.
Singh, Nisha
Cabrera Paz, Francy E.
Oliver, Jonathan D.
Jameson, Julie M
Munderloh, Ulrike G.
Oliva Chávez, Adela S.
Mulenga, Albert
Park, Sangbum
Serre, David
Pedra, Joao H.F.
author_sort Marnin, Liron
collection PubMed
description Hematophagous ectoparasites, such as ticks, rely on impaired wound healing for skin attachment and blood feeding. Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to arthropod-borne diseases. Here, we used orthogonal approaches combining single-cell RNA sequencing (scRNAseq), flow cytometry, murine genetics, and intravital microscopy to demonstrate how tick extracellular vesicles (EVs) disrupt networks involved in tissue repair. Impairment of EVs through silencing of the SNARE protein vamp33 negatively impacted ectoparasite feeding and survival in three medically relevant tick species, including Ixodes scapularis. Furthermore, I. scapularis EVs affected epidermal γδ T cell frequencies and co-receptor expression, which are essential for keratinocyte function. ScRNAseq analysis of the skin epidermis in wildtype animals exposed to vamp33-deficient ticks revealed a unique cluster of keratinocytes with an overrepresentation of pathways connected to wound healing. This biological circuit was further implicated in arthropod fitness when tick EVs inhibited epithelial proliferation through the disruption of phosphoinositide 3-kinase activity and keratinocyte growth factor levels. Collectively, we uncovered a tick-targeted impairment of tissue repair via the resident γδ T cell-keratinocyte axis, which contributes to ectoparasite feeding.
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spelling pubmed-106594232023-11-20 Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy Marnin, Liron Bogale, Haikel N. Laukaitis-Yousey, Hanna J. Valencia, Luisa M. Rolandelli, Agustin O’Neal, Anya J. Ferraz, Camila Rodrigues Schmitter-Sánchez, Axel D. Cuevas, Emily Bencosme Nguyen, Thu-Thuy Leal-Galvan, Brenda Rickert, David M. Bruno, Vincent M. Tays Mendes, M. Samaddar, Sourabh Rainer Butler, L. Singh, Nisha Cabrera Paz, Francy E. Oliver, Jonathan D. Jameson, Julie M Munderloh, Ulrike G. Oliva Chávez, Adela S. Mulenga, Albert Park, Sangbum Serre, David Pedra, Joao H.F. bioRxiv Article Hematophagous ectoparasites, such as ticks, rely on impaired wound healing for skin attachment and blood feeding. Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to arthropod-borne diseases. Here, we used orthogonal approaches combining single-cell RNA sequencing (scRNAseq), flow cytometry, murine genetics, and intravital microscopy to demonstrate how tick extracellular vesicles (EVs) disrupt networks involved in tissue repair. Impairment of EVs through silencing of the SNARE protein vamp33 negatively impacted ectoparasite feeding and survival in three medically relevant tick species, including Ixodes scapularis. Furthermore, I. scapularis EVs affected epidermal γδ T cell frequencies and co-receptor expression, which are essential for keratinocyte function. ScRNAseq analysis of the skin epidermis in wildtype animals exposed to vamp33-deficient ticks revealed a unique cluster of keratinocytes with an overrepresentation of pathways connected to wound healing. This biological circuit was further implicated in arthropod fitness when tick EVs inhibited epithelial proliferation through the disruption of phosphoinositide 3-kinase activity and keratinocyte growth factor levels. Collectively, we uncovered a tick-targeted impairment of tissue repair via the resident γδ T cell-keratinocyte axis, which contributes to ectoparasite feeding. Cold Spring Harbor Laboratory 2023-11-10 /pmc/articles/PMC10659423/ /pubmed/37986907 http://dx.doi.org/10.1101/2023.11.10.566612 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Marnin, Liron
Bogale, Haikel N.
Laukaitis-Yousey, Hanna J.
Valencia, Luisa M.
Rolandelli, Agustin
O’Neal, Anya J.
Ferraz, Camila Rodrigues
Schmitter-Sánchez, Axel D.
Cuevas, Emily Bencosme
Nguyen, Thu-Thuy
Leal-Galvan, Brenda
Rickert, David M.
Bruno, Vincent M.
Tays Mendes, M.
Samaddar, Sourabh
Rainer Butler, L.
Singh, Nisha
Cabrera Paz, Francy E.
Oliver, Jonathan D.
Jameson, Julie M
Munderloh, Ulrike G.
Oliva Chávez, Adela S.
Mulenga, Albert
Park, Sangbum
Serre, David
Pedra, Joao H.F.
Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title_full Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title_fullStr Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title_full_unstemmed Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title_short Tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
title_sort tick extracellular vesicles impair epidermal homeostasis through immune-epithelial networks during hematophagy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10659423/
https://www.ncbi.nlm.nih.gov/pubmed/37986907
http://dx.doi.org/10.1101/2023.11.10.566612
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