Abstract
Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Effective vaccines against most tick-borne pathogens are not currently available. In this study, we characterized a tick histamine release factor (tHRF) from Ixodes scapularis and addressed the vaccine potential of this antigen in the context of tick engorgement and B. burgdorferi transmission. Results from western blotting and quantitative Reverse Transcription-PCR showed that tHRF is secreted in tick saliva, and upregulated in Borrelia burgdorferi-infected ticks. Further, the expression of tHRF was coincident with the rapid feeding phase of the tick, suggesting a role for tHRF in tick engorgement and concomitantly, for efficient B. burgdorferi transmission. Silencing tHRF by RNA interference (RNAi) significantly impaired tick feeding and decreased B. burgdorferi burden in mice. Interfering with tHRF by actively immunizing mice with recombinant tHRF, or passively transferring tHRF antiserum, also markedly reduced the efficiency of tick feeding and B. burgdorferi burden in mice. Recombinant tHRF was able to bind to host basophils and stimulate histamine release. Therefore, we speculate that tHRF might function in vivo to modulate vascular permeability and increase blood flow to the tick bite-site, facilitating tick engorgement. These findings suggest that blocking tHRF might offer a viable strategy to complement ongoing efforts to develop vaccines to block tick feeding and transmission of tick-borne pathogens.
Highlights
Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents
Our results suggested that tick histamine release factor (tHRF) is presented in tick saliva and critical for tick feeding; blocking tHRF markedly reduced the efficiency of tick feeding, and reduced the B. burgdorferi burden in mice
We characterize one of the most highly induced proteins, named tHRF because it shares high homology with a murine histamine release factor (57.1% similarity and 40.1% identity at amino acid level). tHRF mRNA levels were induced during I. scapularis engorgement, and significantly higher in B. burgdorferi-infected, than in uninfected, ticks (p,0.01)
Summary
Ticks are distributed worldwide and affect human and animal health by transmitting diverse infectious agents. Ixodes spp., transmit Borrelia burgdorferi (the Lyme disease agent), Anaplasma phagocytophilum (the cause of human granulocytic anaplasmosis), Babesia microti, and tick-borne encephalitis virus (TBEV), among other pathogens [1,3]. Effective vaccines against most tick-borne pathogens are not currently available and there is an urgent need for the control of ticks and their associated pathogens [4]. B. burgdorferi outer surface protein A has been extensively studied and resulted in an Federal Drug Administration-approved vaccine that was commercially available from 1998 until 2002 [5,6]. One vaccine is approved and available for protection against a tick-borne pathogen – TBEV, which is transmitted by I. ricinus in Northern Europe and Asia [4]
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