It has been demonstrated that impairing protein synthesis using drugs targeted against tRNA amino acid synthetases presents a promising strategy for the treatment of a wide variety of parasitic diseases, including malaria and toxoplasmosis. This is the first study evaluating tRNA synthetases as potential drug targets in ticks. RNAi knock-down of all tested tRNA synthetases had a strong deleterious phenotype on Ixodes ricinus feeding. Our data indicate that tRNA synthetases represent attractive, anti-tick targets warranting the design of selective inhibitors. Further, we tested whether these severely impaired ticks were capable of transmitting Borrelia afzelii spirochaetes. Interestingly, biologically handicapped I. ricinus nymphs transmitted B. afzelii in a manner quantitatively sufficient to develop a systemic infection in mice. These data suggest that initial blood-feeding, despite the incapability of ticks to fully feed and salivate, is sufficient for activating B. afzelii from a dormant to an infectious mode, enabling transmission and dissemination in host tissues.

• Keywords
• Borrelia, Lyme disease, borreliosis, tRNA synthetase, tick, transmission,
• MeSH
• Acaricides pharmacology   MeSH
• Amino Acyl-tRNA Synthetases antagonists & inhibitors   genetics   MeSH
• Borrelia burgdorferi Group MeSH
• Ticks drug effects   microbiology   MeSH
• Humans MeSH
• Lyme Disease drug therapy   microbiology   transmission   MeSH
• Protein Biosynthesis drug effects   MeSH
• Drug Development MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Acaricides MeSH
• Amino Acyl-tRNA Synthetases MeSH

UNLABELLED: Next generation sequencing and proteomics have helped to comprehensively characterize gene expression in tick salivary glands at both the transcriptome and the proteome level. Functional data are, however, lacking. Given that tick salivary secretions are critical to the success of the tick transmission lifecycle and, as a consequence, for host colonization by the pathogens they spread, we thoroughly review here the literature on the known interactions between tick saliva (or tick salivary gland extracts) and the innate and adaptive vertebrate immune system. The information is intended to serve as a reference for functional characterization of the numerous genes and proteins expressed in tick salivary glands with an ultimate goal to develop novel vector and pathogen control strategies. SIGNIFICANCE: We overview all the known interactions of tick saliva with the vertebrate immune system. The provided information is important, given the recent developments in high-throughput transcriptomic and proteomic analysis of gene expression in tick salivary glands, since it may serve as a guideline for the functional characterization of the numerous newly-discovered genes expressed in tick salivary glands.

• Keywords
• Adaptive immunity, Innate immunity, Saliva, Salivary glands, Tick,
• MeSH
• Insect Proteins immunology   MeSH
• Host-Parasite Interactions immunology   MeSH
• Ticks immunology   MeSH
• Models, Immunological MeSH
• Immunity, Innate immunology   MeSH
• Saliva immunology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Research Support, N.I.H., Extramural MeSH
• Research Support, N.I.H., Intramural MeSH
• Names of Substances
• Insect Proteins MeSH

The impact of Ixodes ricinus salivary gland extract (SGE) on inflammatory changes in the skin and draining lymph nodes of mice, elicited by the infection with the important human pathogen, B. afzelii, was determined using flow cytometry. SGE injected together with spirochetes reduced the numbers of leukocytes and gammadelta-T lymphocytes in infected epidermis at early time-points post infection. In draining lymph nodes, the anti-inflammatory effect of SGE was manifested by the decrease of total cell count compared with that in mice treated with inactivated SGE. Changes in subpopulations of immunocompetent cells apparently reflected the effect of SGE on the proliferation of spirochetes in the host. The significance of tick saliva anti-inflammatory effect for saliva activated transmission of B. afzelii is shown.

• MeSH
• Borrelia burgdorferi Group growth & development   MeSH
• Ticks immunology   MeSH
• Skin immunology   pathology   MeSH
• Lyme Disease immunology   pathology   transmission   MeSH
• Lymph Nodes immunology   pathology   MeSH
• Mice, Inbred C57BL MeSH
• Mice MeSH
• Lymphocyte Count MeSH
• Lymphocyte Subsets MeSH
• Salivary Glands immunology   MeSH
• Tissue Extracts immunology   MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Tissue Extracts MeSH