Tick Extracellular Vesicles Undermine Epidermal Wound Healing During Hematophagy

Overview

Journal bioRxiv

Date 2023 Nov 21

PMID 37986907

Authors

Liron Marnin

Luisa M Valencia

Haikel N Bogale

Hanna J Laukaitis-Yousey

Agustin Rolandelli

Camila Rodrigues Ferraz

Anya J ONeal

Axel D Schmitter-Sanchez

Emily Bencosme Cuevas

Thu-Thuy Nguyen

Brenda Leal-Galvan

David M Rickert

M Tays Mendes

Sourabh Samaddar

L Rainer Butler

Nisha Singh

Francy E Cabrera Paz

Jonathan D Oliver

Julie M Jameson

Ulrike G Munderloh

Adela S Oliva Chavez

Albert Mulenga

Sangbum Park

David Serre

Joao H F Pedra

Affiliations

Soon will be listed here.

Abstract

Wound healing has been extensively studied through the lens of inflammatory disorders and cancer, but limited attention has been given to hematophagy and arthropod-borne diseases. Hematophagous ectoparasites, including ticks, subvert the wound healing response to maintain prolonged attachment and facilitate blood-feeding. Here, we unveil a strategy by which extracellular vesicles (EVs) ensure blood-feeding and arthropod survival in three medically relevant tick species. We demonstrate through single cell RNA sequencing and murine genetics that wildtype animals infested with EV-deficient display a unique population of keratinocytes with an overrepresentation of pathways connected to wound healing. Tick feeding affected keratinocyte proliferation in a density-dependent manner, which relied on EVs and dendritic epidermal T cells (DETCs). This occurrence was linked to phosphoinositide 3-kinase activity, keratinocyte growth factor (KGF) and transforming growth factor β (TGF-β) levels. Collectively, we uncovered a strategy employed by a blood-feeding arthropod that impairs the integrity of the epithelial barrier, contributing to ectoparasite fitness.

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