Ticks are parasitic arthropods that suck blood from the surface of most vertebrates. They can transmit a variety of pathogens. The blood sucking of ticks causes varying degrees of damage to the skin of the host.
Proteins related to immune regulation, vascular repair, and wound healing in mammalian skin respond to
tick bites by regulating their expression and post-translational modifications to protect the skin from injury. Phosphorylation of
proteins, as the most common post-translational modification of
proteins, plays an important role in the rapid regulation of cell signal transduction, gene expression and cell cycle. To systematically explore the molecular regulatory mechanisms employed by mammalian skin to resist
tick bites, larval, nymphal, and adult Haemaphysalis longicornis were used to
bite the skin tissues of healthy rabbits in the present study. The quantitative proteomic technology data-independent acquisition was then carried out to investigate in depth the changes in
protein expression and phosphorylation in rabbit skin after
tick bite. The results showed that among the 4034
proteins and 1795 phosphorylated
proteins identified, a total of 202
proteins and 435 phosphorylation sites were changed after H. longicornis
bite. In order to provide convenience for sucking blood, active substances in the saliva of H. longicornis injected into the rabbit's skin can cause the expression level of
trichohyalin and peptidyl
arginine deiminase 3 in the skin of the host downregulate, which can make the host
hair loss and regeneration disorders. At the same time, the active substances in saliva of the H. longicornis led to the phosphorylation of microtubule actin cross-linking factor 1 in the host's skin and further inactivation, so as to delay the healing of the host
wound. In response to
tick bites, the host skin promotes coagulation through high expression of
fibrinogen and
fibronectin, and vascular repair through high expression of
integrin linked kinase and
tenascin C, as well as accelerated phosphorylation of the phosphorylated
protein Nck adaptor protein 1, and wound healing through high expression of
ezrin and
integrin. The upregulation of
proteins such as
coronin,
NADPH oxidase,
calnexin, and
calreticulin and phosphorylation level of IL-4R in the host skin after the H. longicornis
bite indicated that the immune response was playing an important defensive role in response to
tick bites. Meanwhile, we found that the upregulated two
lectins,
mannose receptor C-type 1 and
DC-SIGN, may serve as molecular makers to identify and monitor whether the skin is bitten by ticks. SIGNIFICANCE: Haemaphysalis longicornis are parasitic arthropods that suck blood from the surface of most vertebrates. They can transmit a variety of pathogens and are harmful to humans and livestock. The present study is the first quantitative proteomic study on
protein expression levels in the rabbit skin after
infection by H. longicornis. It is also the first quantitative phosphoproteomic study in the host skin infected by ticks. In this study, we found that
tick bites cause the host
hair loss and regeneration disorders. For resisting
tick bite, the host activates the immune response and initiates vascular repair and wound-healing systems. In addition, some phosphorylated
proteins promote host immunity and vascular repair. These results can help us further understand the defence mechanism of the host against
tick bites, provide a basis for the development of an anti-tick
vaccine, the development of anti-tick drugs, and the diagnosis of
tick-borne diseases.