Marnin Liron, Valencia Luisa M, Bogale Haikel N, Laukaitis-Yousey Hanna J, Rolandelli Agustin, Ferraz Camila Rodrigues, O'Neal Anya J, Schmitter-Sánchez Axel D, Cuevas Emily Bencosme, Nguyen Thu-Thuy, Leal-Galvan Brenda, Rickert David M, Mendes M Tays, Samaddar Sourabh, Butler L Rainer, 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
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
bioRxiv. 2024 Sep 18:2023.11.10.566612. doi: 10.1101/2023.11.10.566612.
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.
伤口愈合已通过炎症性疾病和癌症的视角进行了广泛研究，但对吸血和节肢动物传播疾病的关注有限。包括蜱虫在内的吸血外寄生虫会破坏伤口愈合反应，以维持长时间附着并促进吸血。在这里，我们揭示了一种策略，通过该策略细胞外囊泡（EVs）确保了三种与医学相关的蜱虫物种的吸血和节肢动物存活。我们通过单细胞RNA测序和小鼠遗传学证明，感染了缺乏EVs的野生型动物表现出独特的角质形成细胞群体，与伤口愈合相关的通路过度表达。蜱虫叮咬以密度依赖的方式影响角质形成细胞增殖，这依赖于EVs和树突状表皮T细胞（DETCs）。这种情况与磷酸肌醇3激酶活性、角质形成细胞生长因子（KGF）和转化生长因子β（TGF-β）水平有关。总体而言，我们发现了一种吸血节肢动物采用的策略，该策略损害上皮屏障的完整性，有助于外寄生虫的适应性。
