Dataset Information

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.

ABSTRACT: Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses. For the first time, we report successful isolation of exosomes (small membrane-bound extracellular signaling vesicles) from saliva and salivary glands of partially fed or unfed ixodid ticks. Our data showed a novel role of these in vivo exosomes in the inhibition of wound healing via downregulation of C-X-C motif chemokine ligand 12 (CXCL12) and upregulation of interleukin-8 (IL-8). Cryo-electron microscopy (cryo-EM) analysis revealed that tick saliva and salivary glands are composed of heterogeneous populations of in vivo exosomes with sizes ranging from 30 to 200 nm. Enriched amounts of tick CD63 ortholog protein and heat shock protein 70 (HSP70) were evident in these exosomes. Treatment of human skin keratinocytes (HaCaT cells) with exosomes derived from tick saliva/salivary glands or ISE6 cells dramatically delayed cell migration, wound healing, and repair process. Wound healing is a highly dynamic process with several individualized processes including secretion of cytokines. Cytokine array profiling followed by immunoblotting and quantitative-PCR analysis revealed that HaCaT cells treated with exosomes derived from tick saliva/salivary glands or ISE6 cells showed enhanced IL-8 levels and reduced CXCL12 loads. Inhibition of IL-8 or CXCL12 further delayed exosome-mediated cell migration, wound healing, and repair process, suggesting a skin barrier protection role for these chemokines at the tick bite site. In contrast, exogenous treatment of CXCL12 protein completely restored this delay and enhanced the repair process. Taken together, our study provides novel insights on how tick salivary exosomes secreted in saliva can delay wound healing at the bite site to facilitate successful blood feeding.

SUBMITTER: Zhou W

PROVIDER: S-EPMC7378379 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.

Zhou Wenshuo W Tahir Faizan F Wang Joseph Che-Yen JC Woodson Michael M Sherman Michael B MB Karim Shahid S Neelakanta Girish G Sultana Hameeda H

Frontiers in cell and developmental biology 20200716

Ticks secrete various anti-coagulatory, anti-vasoconstrictory, anti-inflammatory, and anti-platelet aggregation factors in their saliva at the bite site during feeding to evade host immunological surveillance and responses. For the first time, we report successful isolation of exosomes (small membrane-bound extracellular signaling vesicles) from saliva and salivary glands of partially fed or unfed ixodid ticks. Our data showed a novel role of these <i>in vivo</i> exosomes in the inhibition of wo ...[more]

PMID: 32766239

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Project description:Ticks are unique hematophagous arthropods and possess an astounding array of salivary molecules that ensure their unnoticed and prolonged attachment to the host skin. Furthermore, ticks are very effective vectors of a diverse spectrum of pathogens. In order to feed, tick chelicerae cut the host epidermis and their hypostome penetrates through the layers of the skin. As a result of laceration of the skin and rupturing blood vessels, a pool of blood is formed in the dermis, serving for intermittent blood sucking and secretion of saliva. Cutaneous injury caused by tick mouthparts should normally elicit wound healing, a complex biological process coordinated by interaction among different host cells, numerous signalling pathways and by a variety of soluble factors including growth factors. Growth factors, endogenous signalling proteins involved in various biological events, are key players in all phases of the skin repair process. Maintaining feeding site integrity by overcoming sequential phases of wound healing is particularly important for ixodid ticks and is governed by bioactive molecules in their saliva. Tick saliva is a complex mixture of proteins, peptides, and non-peptide molecules and its composition depends on the feeding phase, tick developmental stage, gender and/or the presence/absence of microbial agents. In addition to already demonstrated anti-haemostatic, anti-cytokine and anti-chemokine activities, anti-growth factors activities were also detected in saliva of some tick species. In consequence of counteracting host defences by ticks, tick-borne pathogens can be transmitted to and disseminated in the host. Elucidation of the complex interplay between ticks - pathogens - host cutaneous immunity could lead to improved vector and pathogens control strategies. Additionally, tick saliva bioactive molecules have a promising therapeutic perspective to cure some human diseases associated with dysregulation of specific cytokines/growth factors and alterations in their signalling pathways.

Dataset Information

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.

Publications

Discovery of Exosomes From Tick Saliva and Salivary Glands Reveals Therapeutic Roles for CXCL12 and IL-8 in Wound Healing at the Tick-Human Skin Interface.

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