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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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Related in: MedlinePlus

tHRF antiserum interferes with tick feeding and B. burgdorferi transmission.(A) Weights of B. burgdorferi-infected tick after feeding on tHRF antiserum-immunized, or control, mice. (NRS: normal rabbit serum; rabbit anti-Salp25D antiserum, both used as controls) (B) Spirochete burden in whole I. scapularis nymphs after feeding on tHRF antiserum-immunized, or control, mice. (C) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (D) joints and (E) heart at day 21 post-tick feeding. (F) Weights of uninfected ticks after feeding on tHRF antiserum-immunized, or control, mice. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the NRS controls. Results are a composite of independent experiments.
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ppat-1001205-g003: tHRF antiserum interferes with tick feeding and B. burgdorferi transmission.(A) Weights of B. burgdorferi-infected tick after feeding on tHRF antiserum-immunized, or control, mice. (NRS: normal rabbit serum; rabbit anti-Salp25D antiserum, both used as controls) (B) Spirochete burden in whole I. scapularis nymphs after feeding on tHRF antiserum-immunized, or control, mice. (C) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (D) joints and (E) heart at day 21 post-tick feeding. (F) Weights of uninfected ticks after feeding on tHRF antiserum-immunized, or control, mice. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the NRS controls. Results are a composite of independent experiments.

Mentions: To further examine the importance of tHRF during tick feeding, and its influence on B. burgdorferi transmission, a passive immunization study was performed in naive mice. Groups of 5 mice were administered 200 µl of tHRF antiserum, or control sera (normal rabbit serum or Salp25D antiserum; Salp25D is a tick salivary protein that does not influence tick feeding [23]). One day later, 6 B. burgdorferi-infected ticks were placed on each mouse and tick weights were assessed after 3 days of feeding. Ticks engorging on tHRF antiserum-treated mice weighed significantly less than ticks that fed on control mice (Figure 3A). The spirochete burden in ticks was also substantially lower in I. scapularis that fed on tHRF antiserum-immunized mice (Figure 3B). B. burgdorferi burden was also markedly reduced in tHRF antiserum-immunized mice. The spirochete load in murine skin at day 7 post-infection and in joints and hearts at 3 weeks post-infection was markedly lower in tHRF antiserum-immunized group compared to control serum immunized group (Figure 3, C–E). About 20–27% of the tHRF antiserum-immunized mice (N = 15) were fully protected (based on the absence of a detectable flaB signal in Q-PCR), while 100% of the control animals were infected (N = 30) (Figure 3, C–E).


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)

tHRF antiserum interferes with tick feeding and B. burgdorferi transmission.(A) Weights of B. burgdorferi-infected tick after feeding on tHRF antiserum-immunized, or control, mice. (NRS: normal rabbit serum; rabbit anti-Salp25D antiserum, both used as controls) (B) Spirochete burden in whole I. scapularis nymphs after feeding on tHRF antiserum-immunized, or control, mice. (C) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (D) joints and (E) heart at day 21 post-tick feeding. (F) Weights of uninfected ticks after feeding on tHRF antiserum-immunized, or control, mice. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the NRS controls. Results are a composite of independent experiments.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2991271&req=5

ppat-1001205-g003: tHRF antiserum interferes with tick feeding and B. burgdorferi transmission.(A) Weights of B. burgdorferi-infected tick after feeding on tHRF antiserum-immunized, or control, mice. (NRS: normal rabbit serum; rabbit anti-Salp25D antiserum, both used as controls) (B) Spirochete burden in whole I. scapularis nymphs after feeding on tHRF antiserum-immunized, or control, mice. (C) B. burgdorferi burden in murine skin at day 7 post-tick feeding. Spirochete burden in the (D) joints and (E) heart at day 21 post-tick feeding. (F) Weights of uninfected ticks after feeding on tHRF antiserum-immunized, or control, mice. Horizontal lines and bars represent the mean values ± the SEM. * p<0.05 and ** p<0.01, when compared with the NRS controls. Results are a composite of independent experiments.
Mentions: To further examine the importance of tHRF during tick feeding, and its influence on B. burgdorferi transmission, a passive immunization study was performed in naive mice. Groups of 5 mice were administered 200 µl of tHRF antiserum, or control sera (normal rabbit serum or Salp25D antiserum; Salp25D is a tick salivary protein that does not influence tick feeding [23]). One day later, 6 B. burgdorferi-infected ticks were placed on each mouse and tick weights were assessed after 3 days of feeding. Ticks engorging on tHRF antiserum-treated mice weighed significantly less than ticks that fed on control mice (Figure 3A). The spirochete burden in ticks was also substantially lower in I. scapularis that fed on tHRF antiserum-immunized mice (Figure 3B). B. burgdorferi burden was also markedly reduced in tHRF antiserum-immunized mice. The spirochete load in murine skin at day 7 post-infection and in joints and hearts at 3 weeks post-infection was markedly lower in tHRF antiserum-immunized group compared to control serum immunized group (Figure 3, C–E). About 20–27% of the tHRF antiserum-immunized mice (N = 15) were fully protected (based on the absence of a detectable flaB signal in Q-PCR), while 100% of the control animals were infected (N = 30) (Figure 3, C–E).

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