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Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.

Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E - PLoS Pathog. (2010)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.

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.

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Tick feeding and B. burgdorferi transmission was significantly impaired in tHRF immunized mice.(A) tHRF probed with sera from mice or rabbits actively immunized with tHRF. (B) Weights of B. burgdorferi uninfected or (C) infected tick after feeding on tHRF-immunized, or control, mice. (D) Spirochete burden in whole I. scapularis after feeding on tHRF-immunized, or control, mice. (E) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (F) joints and (G) heart at day 21 post-tick feeding. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the control group. Results are pooled from 3 independent experiments.
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ppat-1001205-g004: Tick feeding and B. burgdorferi transmission was significantly impaired in tHRF immunized mice.(A) tHRF probed with sera from mice or rabbits actively immunized with tHRF. (B) Weights of B. burgdorferi uninfected or (C) infected tick after feeding on tHRF-immunized, or control, mice. (D) Spirochete burden in whole I. scapularis after feeding on tHRF-immunized, or control, mice. (E) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (F) joints and (G) heart at day 21 post-tick feeding. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the control group. Results are pooled from 3 independent experiments.

Mentions: We then assessed the ability of the ticks to feed on mice actively immunized with tHRF. Group of 5 mice were immunized with recombinant tHRF, or adjuvant (control). Immunoblots confirmed that mice generated antibodies against tHRF following active immunization (Figure 4A). The tick weights were significantly decreased when B. burgdorferi-infected, or uninfected, nymphs fed on tHRF immunized mice compared to ticks that fed on control mice (Figure 4, B and C). The spirochete load was also markedly reduced in ticks fed on tHRF-immunized mice (Figure 4D) and in murine skin (at day 7 post-infection) (Figure 4E) and in joints and hearts (at 3 weeks post-infection) in the tHRF-immunized group compared to that in control mice (Figure 4, F–G). 20–33% of tHRF immunized mice (N = 15) were PCR negative, while 100% of the mice in the control groups (N = 15) were PCR positive for B. burgdorferi flaB amplicon (Figure 4, E–G).


Tick histamine release factor is critical for Ixodes scapularis engorgement and transmission of the lyme disease agent.

Dai J, Narasimhan S, Zhang L, Liu L, Wang P, Fikrig E - PLoS Pathog. (2010)

Tick feeding and B. burgdorferi transmission was significantly impaired in tHRF immunized mice.(A) tHRF probed with sera from mice or rabbits actively immunized with tHRF. (B) Weights of B. burgdorferi uninfected or (C) infected tick after feeding on tHRF-immunized, or control, mice. (D) Spirochete burden in whole I. scapularis after feeding on tHRF-immunized, or control, mice. (E) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (F) joints and (G) heart at day 21 post-tick feeding. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the control group. Results are pooled from 3 independent experiments.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2991271&req=5

ppat-1001205-g004: Tick feeding and B. burgdorferi transmission was significantly impaired in tHRF immunized mice.(A) tHRF probed with sera from mice or rabbits actively immunized with tHRF. (B) Weights of B. burgdorferi uninfected or (C) infected tick after feeding on tHRF-immunized, or control, mice. (D) Spirochete burden in whole I. scapularis after feeding on tHRF-immunized, or control, mice. (E) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (F) joints and (G) heart at day 21 post-tick feeding. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the control group. Results are pooled from 3 independent experiments.
Mentions: We then assessed the ability of the ticks to feed on mice actively immunized with tHRF. Group of 5 mice were immunized with recombinant tHRF, or adjuvant (control). Immunoblots confirmed that mice generated antibodies against tHRF following active immunization (Figure 4A). The tick weights were significantly decreased when B. burgdorferi-infected, or uninfected, nymphs fed on tHRF immunized mice compared to ticks that fed on control mice (Figure 4, B and C). The spirochete load was also markedly reduced in ticks fed on tHRF-immunized mice (Figure 4D) and in murine skin (at day 7 post-infection) (Figure 4E) and in joints and hearts (at 3 weeks post-infection) in the tHRF-immunized group compared to that in control mice (Figure 4, F–G). 20–33% of tHRF immunized mice (N = 15) were PCR negative, while 100% of the mice in the control groups (N = 15) were PCR positive for B. burgdorferi flaB amplicon (Figure 4, E–G).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.

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.

Show MeSH
Related in: MedlinePlus